Oligonucleotides antisense. Medical search

Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)

RNA molecules which hybridize to complementary sequences in either RNA or DNA altering the function of the latter. Endogenous antisense RNAs function as regulators of gene expression by a variety of mechanisms. Synthetic antisense RNAs are used to effect the functioning of specific genes for investigative or therapeutic purposes.

DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes.

Short fragments of DNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

Nucleic acids which hybridize to complementary sequences in other target nucleic acids causing the function of the latter to be affected.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Short fragments of RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.

A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A group of ribonucleotides (up to 12) in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.

Modified oligonucleotides in which one of the oxygens of the phosphate group is replaced with a sulfur atom.

Nucleotides in which the base moiety is substituted with one or more sulfur atoms.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.

Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.

A ribonuclease that specifically cleaves the RNA moiety of RNA:DNA hybrids. It has been isolated from a wide variety of prokaryotic and eukaryotic organisms as well as RETROVIRUSES.

A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

Synthetic analogs of NUCLEIC ACIDS composed of morpholine ring derivatives (MORPHOLINES) linked by phosphorodimidates. One standard DNA nucleic acid base (ADENINE; GUANINE; CYTOSINE; OR THYMINE) is bound to each morpholine ring.

DNA analogs containing neutral amide backbone linkages composed of aminoethyl glycine units instead of the usual phosphodiester linkage of deoxyribose groups. Peptide nucleic acids have high biological stability and higher affinity for complementary DNA or RNA sequences than analogous DNA oligomers.

Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

Established cell cultures that have the potential to propagate indefinitely.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.

High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.

A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.

The rate dynamics in chemical or physical systems.

Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

An enzyme catalyzing the endonucleolytic cleavage of RNA at the 3'-position of a guanylate residue. EC 3.1.27.3.

A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-.

One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.

Ribonucleic acid that makes up the genetic material of viruses.

Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Linear furanocoumarins which are found in many PLANTS, especially UMBELLIFERAE and RUTACEAE, as well as PSORALEA from which they were originally discovered. They can intercalate DNA and, in an UV-initiated reaction of the furan portion, alkylate PYRIMIDINES, resulting in PHOTOSENSITIVITY DISORDERS.

The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.

The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.

Double-stranded nucleic acid molecules (DNA-DNA or DNA-RNA) which contain regions of nucleotide mismatches (non-complementary). In vivo, these heteroduplexes can result from mutation or genetic recombination; in vitro, they are formed by nucleic acid hybridization. Electron microscopic analysis of the resulting heteroduplexes facilitates the mapping of regions of base sequence homology of nucleic acids.

Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.

Agents that are capable of inserting themselves between the successive bases in DNA, thus kinking, uncoiling or otherwise deforming it and therefore preventing its proper functioning. They are used in the study of DNA.

Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.

The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.

Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.

Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

A cell line derived from cultured tumor cells.

Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Biologically functional sequences of DNA chemically synthesized in vitro.

DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.

The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.

The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).

The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.

Inorganic derivatives of phosphoric acid (H3PO4). Note that organic derivatives of phosphoric acids are listed under ORGANOPHOSPHATES.

Interruption or suppression of the expression of a gene at transcriptional or translational levels.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.

The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.

The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.

A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)

Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.

The chemical and physical integrity of a pharmaceutical product.

Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.

A group of 13 or more deoxyribonucleotides in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.

Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity.

Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.

The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.

The relationship between the dose of an administered drug and the response of the organism to the drug.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.

Elements of limited time intervals, contributing to particular results or situations.

A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.

A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.

The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.

Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.

The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.

Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.

A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.

RNA, usually prepared by transcription from cloned DNA, which complements a specific mRNA or DNA and is generally used for studies of virus genes, distribution of specific RNA in tissues and cells, integration of viral DNA into genomes, transcription, etc. Whereas DNA PROBES are preferred for use at a more macroscopic level for detection of the presence of DNA/RNA from specific species or subspecies, RNA probes are preferred for genetic studies. Conventional labels for the RNA probe include radioisotope labels 32P and 125I and the chemical label biotin. RNA probes may be further divided by category into plus-sense RNA probes, minus-sense RNA probes, and antisense RNA probes.

Ribonucleic acid in bacteria having regulatory and catalytic roles as well as involvement in protein synthesis.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

A group of 13 or more ribonucleotides in which the phosphate residues of each ribonucleotide act as bridges in forming diester linkages between the ribose moieties.

Proteins prepared by recombinant DNA technology.

Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.

A group of thymine nucleotides in which the phosphate residues of each thymine nucleotide act as bridges in forming diester linkages between the deoxyribose moieties.

RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.

A pyrimidine base that is a fundamental unit of nucleic acids.

A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.

Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.

Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.

Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.

RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.

Fluorescent probe capable of being conjugated to tissue and proteins. It is used as a label in fluorescent antibody staining procedures as well as protein- and amino acid-binding techniques.

A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.

A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.

Deoxyribonucleic acid that makes up the genetic material of viruses.

Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.

A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)

The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.

The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.

Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)

The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.

Proteins obtained from various species of Xenopus. Included here are proteins from the African clawed frog (XENOPUS LAEVIS). Many of these proteins have been the subject of scientific investigations in the area of MORPHOGENESIS and development.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.

Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES.

Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.

Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES.

DNA or RNA bound to a substrate thereby having fixed positions.

Synthetic transcripts of a specific DNA molecule or fragment, made by an in vitro transcription system. This cRNA can be labeled with radioactive uracil and then used as a probe. (King & Stansfield, A Dictionary of Genetics, 4th ed)

Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)

The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.

A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.

A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

Molecules of DNA that possess enzymatic activity.

Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.

The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.

Carbon-containing thiophosphoric acid derivatives. Included under this heading are compounds that have carbon bound to either SULFUR atom, or the OXYGEN atom of the SPO3 core structure.

A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.

Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).

That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.

Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.

Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).

RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.

A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.

A family of enzymes that catalyze the endonucleolytic cleavage of RNA. It includes EC 3.1.26.-, EC 3.1.27.-, EC 3.1.30.-, and EC 3.1.31.-.

Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.

An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)

The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.

Hard, amorphous, brittle, inorganic, usually transparent, polymerous silicate of basic oxides, usually potassium or sodium. It is used in the form of hard sheets, vessels, tubing, fibers, ceramics, beads, etc.

PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.

The functional hereditary units of VIRUSES.

A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.

Deoxyribonucleic acid that makes up the genetic material of bacteria.

A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.

Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.

Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Transport proteins that carry specific substances in the blood or across cell membranes.

Histochemical localization of immunoreactive substances using labeled antibodies as reagents.

Substances that inhibit or prevent the proliferation of NEOPLASMS.

A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.

A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).

Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.

Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.

Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)

Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

2-Amino-1,5-dihydro-4,6-pteridinedione. Pigment first discovered in butterfly wings and widely distributed in plants and animals.

Chromosomal, biochemical, intracellular, and other methods used in the study of genetics.

The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.

A technique which uses synthetic oligonucleotides to direct the cell's inherent DNA repair system to correct a mutation at a specific site in an episome or chromosome.

Enzymes which catalyze the hydrolases of ester bonds within DNA. EC 3.1.-.

A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.

Experimental transplantation of neoplasms in laboratory animals for research purposes.

A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.

Requirement of a novel gene, Xin, in cardiac morphogenesis. (1/4678)

A novel gene, Xin, from chick (cXin) and mouse (mXin) embryonic hearts, may be required for cardiac morphogenesis and looping. Both cloned cDNAs have a single open reading frame, encoding proteins with 2,562 and 1,677 amino acids for cXin and mXin, respectively. The derived amino acid sequences share 46% similarity. The overall domain structures of the predicted cXin and mXin proteins, including proline-rich regions, 16 amino acid repeats, DNA-binding domains, SH3-binding motifs and nuclear localization signals, are highly conserved. Northern blot analyses detect a single message of 8.9 and 5.8 kilo base (kb) from both cardiac and skeletal muscle of chick and mouse, respectively. In situ hybridization reveals that the cXin gene is specifically expressed in cardiac progenitor cells of chick embryos as early as stage 8, prior to heart tube formation. cXin continues to be expressed in the myocardium of developing hearts. By stage 15, cXin expression is also detected in the myotomes of developing somites. Immunofluorescence microscopy reveals that the mXin protein is colocalized with N-cadherin and connexin-43 in the intercalated discs of adult mouse hearts. Incubation of stage 6 chick embryos with cXin antisense oligonucleotides results in abnormal cardiac morphogenesis and an alteration of cardiac looping. The myocardium of the affected hearts becomes thickened and tends to form multiple invaginations into the heart cavity. This abnormal cellular process may account in part for the abnormal looping. cXin expression can be induced by bone morphogenetic protein (BMP) in explants of anterior medial mesoendoderm from stage 6 chick embryos, a tissue that is normally non-cardiogenic. This induction occurs following the BMP-mediated induction of two cardiac-restricted transcription factors, Nkx2.5 and MEF2C. Furthermore, either MEF2C or Nkx2.5 can transactivate a luciferase reporter driven by the mXin promoter in mouse fibroblasts. These results suggest that Xin may participate in a BMP-Nkx2.5-MEF2C pathway to control cardiac morphogenesis and looping. (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (2/4678)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth. (+info)

The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells. (3/4678)

We have previously found that epidermal growth factor (EGF) mediates growth through the Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) pathway in A549 human lung carcinoma cells. As observed here, EGF treatment also greatly enhances the tumorigenicity of A549 cells, suggesting an important role for JNK in cancer cell growth (F. Bost, R. McKay, N. Dean, and D. Mercola, J. Biol. Chem. 272:33422-33429, 1997). Several isoforms families of JNK, JNK1, JNK2, and JNK3, have been isolated; they arise from alternative splicing of three different genes and have distinct substrate binding properties. Here we have used specific phosphorothioate oligonucleotides targeted against the two major isoforms, JNK1 and JNK2, to discriminate their roles in EGF-induced transformation. Multiple antisense sequences have been screened, and two high-affinity and specific candidates have been identified. Antisense JNK1 eliminated steady-state mRNA and JNK1 protein expression with a 50% effective concentration (EC50) of <0.1 microM but did not alter JNK2 mRNA or protein levels. Conversely, antisense JNK2 specifically eliminated JNK2 steady-state mRNA and protein expression with an EC50 of 0.1 microM. Antisense JNK1 and antisense JNK2 inhibited by 40 and 70%, respectively, EGF-induced total JNK activity, whereas sense and scrambled-sequence control oligonucleotides had no effect. The elimination of mRNA, protein, and JNK activities lasted 48 and 72 h following a single Lipofectin treatment with antisense JNK1 and JNK2, respectively, indicating sufficient duration for examining the impact of specific elimination on the phenotype. Direct proliferation assays demonstrated that antisense JNK2 inhibited EGF-induced doubling of growth as well as the combination of active antisense oligonucleotides did. EGF treatment also induced colony formation in soft agar. This effect was completely inhibited by antisense JNK2 and combined-antisense treatment but not altered by antisense JNK1 alone. These results show that EGF doubles the proliferation (growth in soft agar as well as tumorigenicity in athymic mice) of A549 lung carcinoma cells and that the JNK2 isoform but not JNK1 is utilized for mediating the effects of EGF. This study represents the first demonstration of a cellular phenotype regulated by a JNK isoform family, JNK2. (+info)

Upstream region of rat serum albumin gene promoter contributes to promoter activity: presence of functional binding site for hepatocyte nuclear factor-3. (4/4678)

Transcription of the serum albumin gene occurs almost exclusively in the liver and is controlled in part by a strong liver-specific promoter. The upstream region of the serum albumin gene promoter is highly conserved among species and is footprinted in vitro by a number of nuclear proteins. However, the role of the upstream promoter region in regulating transcription and the identity of the transcription factors that bind to this region have not been established. In the present study, deletion analysis of the rat serum albumin promoter in transiently transfected HepG2 cells demonstrated that elimination of the region between -207 and -153 bp caused a two-fold decrease in promoter activity (P<0.05). Additional analysis of the -207 to -124 bp promoter interval led to the identification of two potential binding sites for hepatocyte nuclear factor-3 (HNF-3) located at -168 to -157 bp (site X) and -145 to -134 bp (site Y). Electrophoretic mobility-shift assays performed with the HNF-3 X and Y sites demonstrated that both sites are capable of binding HNF-3alpha and HNF-3beta. Placement of a single copy of the HNF-3 X site upstream from a minimal promoter increased promoter activity by about four-fold in HepG2 cells, and the reporter construct containing this site could be transactivated if co-transfected with an HNF-3 expression construct. Furthermore, inactivation of the HNF-3 X site by site-directed mutagenesis within the context of the -261 bp albumin promoter construct resulted in a 40% decrease in transcription (P<0.05). These results indicate that the positive effect of the -207 to -153 bp promoter interval is attributable to the presence of the HNF-3 X site within this interval. Additional results obtained with transfected HepG2 cells suggest that the HNF-3 Y site plays a lesser role in activation of transcription than the X site. (+info)

Hyperoxia induces the neuronal differentiated phenotype of PC12 cells via a sustained activity of mitogen-activated protein kinase induced by Bcl-2. (5/4678)

We previously reported that rat pheochromocytoma PC12 cells express the neuronal differentiated phenotype under hyperoxia through the production of reactive oxygen species (ROS). In the present study, we found that in this phenotype, Bcl-2, an apoptosis inhibitor, affects mitogen-activated protein (MAP)-kinase activity, which is known as a key enzyme of the signal-transduction cascade for differentiation. When PC12 cells were cultured under hyperoxia, a rapid increase in MAP-kinase activity, including that of both p42 and p44, was observed. Although the activity level then decreased quickly, activity higher than the control level was observed for 48 h. PD98059, an inhibitor of MAP kinase, suppressed the hyperoxia-induced neurite extensions, suggesting the involvement of MAP-kinase activity in the mechanism of differentiation induced by ROS. An elevation of Bcl-2 expression was observed after culturing PC12 cells for 24 h under hyperoxia. This Bcl-2 elevation was not affected by treatment with PD98059, suggesting that it did not directly induce neurite extension under hyperoxia. However, the blockade of the Bcl-2 elevation by an antisense oligonucleotide inhibited the sustained MAP-kinase activity and neurite extensions under hyperoxia. Further, in PC12 cells highly expressing Bcl-2, the sustained MAP-kinase activity and neurite extensions under hyperoxia were enhanced. These results suggested that MAP kinase is activated through the production of ROS, and the subsequent elevation of Bcl-2 expression sustains the MAP-kinase activity, resulting in the induction of the neuronal-differentiation phenotype of PC12 cells under hyperoxia. (+info)

Simultaneous antisense inhibition of two starch-synthase isoforms in potato tubers leads to accumulation of grossly modified amylopectin. (6/4678)

A chimaeric antisense construct was used to reduce the activities of the two major starch-synthase isoforms in potato tubers simultaneously. A range of reductions in total starch-synthase activities were found in the resulting transgenic plants, up to a maximum of 90% inhibition. The reduction in starch-synthase activity had a profound effect on the starch granules, which became extremely distorted in appearance compared with the control lines. Analysis of the starch indicated that the amounts produced in the tubers, and the amylose content of the starch, were not affected by the reduction in activity. In order to understand why the starch granules were distorted, amylopectin was isolated and the constituent chain lengths analysed. This indicated that the amylopectin was very different to that of the control. It contained more chains of fewer than 15 glucose units in length, and fewer of between 15 and 80 glucose units. In addition, the amylopectin contained more very long chains. Amylopectin from plants repressed in just one of the activities of the two starch-synthase isoforms, which we have reported upon previously, were also analysed. Using a technique different to that used previously we show that both isoforms also affect the amylopectin, but in a way that is different to when both isoforms are repressed together. (+info)

Regulation of cardiac L-type Ca2+ channel by coexpression of G(alpha s) in Xenopus oocytes. (7/4678)

Activation of G(alpha s) via beta-adrenergic receptors enhances the activity of cardiac voltage-dependent Ca2+ channels of the L-type, mainly via protein kinase A (PKA)-dependent phosphorylation. Contribution of a PKA-independent effect of G(alpha s) has been proposed but remains controversial. We demonstrate that, in Xenopus oocytes, antisense knockdown of endogenous G(alpha s) reduced, whereas coexpression of G(alpha s) enhanced, currents via expressed cardiac L-type channels, independently of the presence of the auxiliary subunits alpha2/delta or beta2A. Coexpression of G(alpha s) did not increase the amount of alpha1C protein in whole oocytes or in the plasma membrane (measured immunochemically). Activation of coexpressed beta2 adrenergic receptors did not cause a detectable enhancement of channel activity; rather, a small cAMP-dependent decrease was observed. We conclude that coexpression of G(alpha s), but not its acute activation via beta-adrenergic receptors, enhances the activity of the cardiac L-type Ca2+ channel via a PKA-independent effect on the alpha1C subunit. (+info)

Oligonucleotide-europium complex conjugate designed to cleave the 5' cap structure of the ICAM-1 transcript potentiates antisense activity in cells. (8/4678)

The 5' cap structure of mRNA is a N7 methylated guanosine residue that is linked by a 5'-5' triphosphate linkage to the 5'-terminus of cellular and viral RNAs synthesized by RNA polymerase II. This unique structure facilitates several processes of mRNA metabolism, including splicing, nucleocytoplasmic transport,initiation of translation, and degradation. Previous research has demonstrated that the lanthanide macrocycle complex, Eu(THED)3+, effectively cleaves the 5' cap structure of mRNA in solution by nucleophilic attack of the triphosphate linkage via the metal-activated hydroxyethyl group of the THED ligand. This report shows that attachment of a Eu(THED)3+analog to the 3'-terminus of an antisense oligonucleotide, which targets the 5'-terminus of the intercellular adhesion molecule 1 mRNA, potentiates the inhibitory activity of the antisense oligonucleotide in cytokine-treatedendothelial cells. (+info)

The antisense field anticipated that the approval of fomivirsen marked the beginning of a new age of antisense drug treatments ... Offord, Catherine (December 1, 2016). "Oligonucleotide Therapeutics Near Approval". The Scientist. "Company News; Isis ... Clinical trials of antisense therapeutics by Isis and others in the early 2000s were also plagued by lack of efficacy and ... It was approved by the FDA for CMV in Aug 1998, and was the first antisense drug that was approved. Novartis withdrew the ...

https://en.wikipedia.org/wiki/Ionis_Pharmaceuticals

The potential of antisense oligonucleotides to treat neurodegenerative diseases was reviewed by Tabrizi in Science in 2020. ... "Full Results from Huntingtin Lowering Antisense Oligonucleotides Trial now published". UCL Queen Square Institute of Neurology ... Leavitt, Blair R.; Tabrizi, Sarah J. (2020-03-27). "Antisense oligonucleotides for neurodegeneration". Science. 367 (6485): ... or huntingtin-lowering antisense oligonucleotide (ASO) drug in Huntington's disease patients. The announcement of the 'top line ...

https://en.wikipedia.org/wiki/Sarah_Tabrizi

In vivo applications of antisense oligonucleotides showed that toxicity is largely due to impurities in the oligonucleotide ... Brysch, Wolfgang; Schlingensiepen, Karl-Hermann (1994). "Design and application of antisense oligonucleotides in cell culture, ... Lebedeva, Irina; Stein, CA (2001). "Antisense oligonucleotides: promise and reality". Annual Review of Pharmacology and ... "Nanoparticulate systems for the delivery of antisense oligonucleotides". Advanced Drug Delivery Reviews. 47 (1): 99-112. doi: ...

https://en.wikipedia.org/wiki/Computational_gene

Woolf TM, Melton DA, Jennings CG (August 1992). "Specificity of antisense oligonucleotides in vivo". Proceedings of the ... The remaining anti-sense strand-RISC complex can then bind to target mRNAs for initiating transcriptional silencing. It has ... To begin the process, one of the two siRNA strands, the guide strand (anti-sense strand), will be loaded into the RISC while ... Since genes are read in both directions, there exists a possibility that even if the intended antisense siRNA strand is read ...

https://en.wikipedia.org/wiki/Small_interfering_RNA

Antisense therapy targets gene sequences using antisense oligonucleotides by binding the ASO to the mRNA strand. This creates ... Custirsen is a second-generation phosphorothioate antisense oligonucleotide. Phosphorothioates are oligonucleotides with a ... An antisense oligonucleotide (ASO) is a single-strand DNA sequence complementary to a desired messenger RNA (mRNA) sequence. ... It is an antisense oligonucleotide (ASO) targeting clusterin expression. In metastatic prostate cancer, custirsen showed no ...

https://en.wikipedia.org/wiki/Custirsen

In addition, when antisense oligonucleotides were used to target an HD-associated SNP in mice, there was a 50% decrease in the ... The antisense oligonucleotides can affect gene expression in two ways: by using an RNase H-dependent mechanism or by using a ... Ribozymes, antisense oligonucleotides, and more recently RNAi have been used to target mRNA molecules involved in asthma. These ... Both antisense oligonucleotides and siRNA molecules can potentially bind to the wrong mRNA molecule. Thus, researchers are ...

https://en.wikipedia.org/wiki/Gene_silencing

... is an oligonucleotide capable of antisense interactions with mRNA of human papillomavirus. It has been investigated ... "In vitro pharmacokinetics of phosphorothioate antisense oligonucleotides". The Journal of Pharmacology and Experimental ...

https://en.wikipedia.org/wiki/Afovirsen

"Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". European ... An antisense oligonucleotide drug, oblimersen (G3139), was developed by Genta Incorporated to target Bcl-2. An antisense DNA or ... Human lymphoma cell proliferation (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon ... An antisense drug is a short sequence of RNA that hybridises with and inactivates mRNA, preventing the protein from being ...

https://en.wikipedia.org/wiki/Bcl-2

"Potential roles of antisense oligonucleotides in cancer therapy. The example of Bcl-2 antisense oligonucleotides". European ... An antisense oligonucleotide drug Genasense (G3139) has been developed by Genta Incorporated to target Bcl-2. An antisense DNA ... Oblimersen (INN, trade name Genasense; also known as Augmerosen and bcl-2 antisense oligodeoxynucleotide G3139) is an antisense ... It was shown that the proliferation of human lymphoma cells (with t(14;18) translocation) could be inhibited by antisense RNA ...

https://en.wikipedia.org/wiki/Oblimersen

Evers MM, Toonen LJ, van Roon-Mom WM (June 2015). "Antisense oligonucleotides in therapy for neurodegenerative disorders". ... antisense oligonucleotide therapy, which uses single strands of RNA complementary to the target to prevent the target from ... Instead of complementary 'antisense' strands of RNA, RNAi uses very small double stranded segments of RNA called small ... "An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases". BMC Molecular Biology. 13 (1): 6. doi: ...

https://en.wikipedia.org/wiki/Spinocerebellar_ataxia_type_1

Antisense oligonucleotides: TPI ASM8. IL-6. *Agonists: Atexakin alfa. *Interleukin 6. *Antibodies: ARGX-109 ...

https://en.wikipedia.org/wiki/Interleukin_8_receptor,_alpha

Antisense oligonucleotides: IONIS-GCCRRx (ISIS-426115). See also. Receptor/signaling modulators. Glucocorticoids and ...

https://en.wikipedia.org/wiki/Solu-Medrol

Antisense oligonucleotides: Atesidorsen. *Binding proteins: GHBP. GHIH. (somatostatin). *Agonists: BIM-23052. *CH-275 ...

https://en.wikipedia.org/wiki/GHRP-6

Antisense oligonucleotides: TPI ASM8. IL-6. *Agonists: Atexakin alfa. *Interleukin 6. *Antibodies: ARGX-109 ...

https://en.wikipedia.org/wiki/Interleukin_24

Antisense oligonucleotides: Atesidorsen. *Binding proteins: GHBP. GHIH. (somatostatin). *Agonists: BIM-23052. *CH-275 ...

https://en.wikipedia.org/wiki/Somatotropin

Antisense oligonucleotides: IONIS-GCCRRx (ISIS-426115). See also. Receptor/signaling modulators. Glucocorticoids and ...

https://en.wikipedia.org/wiki/Cortisol

The compound is a 'second-generation' antisense oligonucleotide; the nucleotides are linked with phosphorothioate linkages ... a second-generation antisense oligonucleotide inhibitor of apolipoprotein B". Clinical Pharmacokinetics. 54 (2): 133-146. doi: ...

https://en.wikipedia.org/wiki/Mipomersen

Wahlestedt, Claes (February 1994). "Antisense oligonucleotide strategies in neuropharmacology". Trends Pharmacol Sci. 15 (2): ... Summerton J (December 1999). "Morpholino antisense oligomers: the case for an RNase H-independent structural type". Biochimica ... If the change in gene expression is caused by an oligonucleotide binding to an mRNA or temporarily binding to a gene, this ... by morpholino oligos or other RNase-H independent antisense). The most direct use of transient knockdowns is for learning about ...

https://en.wikipedia.org/wiki/Gene_knockdown

Use of Antisense oligonucleotides to slow progression of CJD are being investigated and have shown promising activity in mice ... "Prion disease in mice treated successfully with antisense oligonucleotides". News-Medical.net. 2019-08-01. Retrieved 2019-08-09 ...

https://en.wikipedia.org/wiki/Creutzfeldt–Jakob_disease

Frieden, M. (2003-11-01). "Expanding the design horizon of antisense oligonucleotides with alpha-L-LNA". Nucleic Acids Research ... Kurreck, J. (2002-05-01). "Design of antisense oligonucleotides stabilized by locked nucleic acids". Nucleic Acids Research. 30 ... Using LNA based oligonucleotides therapeutically is an emerging field in biotechnology. A variety of LNA oligonucleotides have ... LNA-modified oligonucleotides is a promising option in the development of therapeutics due to its high stability in biological ...

https://en.wikipedia.org/wiki/Locked_nucleic_acid

Hwang J, Yokota T (October 2019). "Recent advancements in exon-skipping therapies using antisense oligonucleotides and genome ... Viltolarsen is a Morpholino antisense oligonucleotide. The most common side effects include upper respiratory tract infection, ... has been observed after administration of some antisense oligonucleotides. Viltolarsen was evaluated in two clinical studies ... Dzierlega K, Yokota T (June 2020). "Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy". Gene ...

https://en.wikipedia.org/wiki/Viltolarsen

The mechanism behind exon skipping is a mutation specific antisense oligonucleotide (AON). An antisense oligonucleotide is a ... A third antisense oligonucleotide, viltolarsen (Viltepso), targeting dystrophin exon 53 was approved for medical use in the ... Harding PL, Fall AM, Honeyman K, Fletcher S, Wilton SD (January 2007). "The influence of antisense oligonucleotide length on ... Antisense therapy Wahl M (1 October 2011). "Exon Skipping in DMD: What Is It and Whom Can It Help?". Quest Magazine Online. ...

https://en.wikipedia.org/wiki/Exon_skipping

Chen, Inês (November 19, 2019). "An antisense oligonucleotide splicing modulator to treat spinal muscular atrophy". Nature ... Spinraza is an oligonucleotide that works to activate SMN2 to make more SMN protein in SMA patients. In 2015, the families of ... work on the SMN2 gene for SMA therapy that focus specifically on exon 7 inclusion to work in conjunction with oligonucleotide ...

https://en.wikipedia.org/wiki/Alberto_Kornblihtt

Sazani P, Kang SH, Maier MA, Wei C, Dillman J, Summerton J, Manoharan M, Kole R (October 2001). "Nuclear antisense effects of ... neutral, anionic and cationic oligonucleotide analogs". Nucleic Acids Research. 29 (19): 3965-74. doi:10.1093/nar/29.19.3965. ... Splicing events can be experimentally altered by binding steric-blocking antisense oligos such as Morpholinos or Peptide ...

https://en.wikipedia.org/wiki/RNA_splicing

"Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides". Journal of Immunology. 152 (7): ... Alicaforsen is a first generation antisense oligodeoxynucleotide designed to bind specifically to the human ICAM-1 messenger ...

https://en.wikipedia.org/wiki/Inflammatory_bowel_disease

Oligonucleotide synthesis Nucleic acid analogue Heasman J (March 2002). "Morpholino oligos: making sense of antisense?". ... Jubin R (2004). Optimizing electroporation conditions for intracellular delivery of Morpholino antisense oligonucleotides ... Summerton J, Weller D (June 1997). "Morpholino antisense oligomers: design, preparation, and properties". Antisense & Nucleic ... is corrected in vitro by morpholino antisense oligonucleotides". Human Mutation. 27 (5): 420-6. doi:10.1002/humu.20303. PMID ...

https://en.wikipedia.org/wiki/Morpholino

The goal of using these antisense oligonucleotides are the decrease in protein expression of a specific target usually by the ... Antisense oligonucleotides (ASOs) are small strand single stranded oligodeoxynucleotides approximately 15-20 nucleic acids in ... The most advanced available therapies aim to target mutated gene expression by using antisense oligonucleotides (ASO) or RNA ... Rinaldi, Carlo; Wood, Matthew J. A. (January 2018). "Antisense oligonucleotides: the next frontier for treatment of ...

https://en.wikipedia.org/wiki/Trinucleotide_repeat_expansion

Antisense oligonucleotides (oligos), structural analogs of DNA, are the basis of a potential treatment for 10% of people with ... The antisense oligonucleotide golodirsen (Vyondys 53) was approved for medical use in the United States in 2019, for the ... The Morpholino antisense oligonucleotide viltolarsen (Viltepso) was approved for medical use in the United States in August ... Wilton SD, Fall AM, Harding PL, McClorey G, Coleman C, Fletcher S (July 2007). "Antisense oligonucleotide-induced exon skipping ...

https://en.wikipedia.org/wiki/Duchenne_muscular_dystrophy

Milner, N.; Mir, K. U.; Southern, E. M. (1997). "Selecting effective antisense reagents on combinatorial oligonucleotide arrays ... Maskos, U.; Southern, E. M. (1992). "Oligonucleotide hybridisations on glass supports: A novel linker for oligonucleotide ... synthesis and hybridisation properties of oligonucleotides synthesised in situ". Nucleic Acids Research. 20 (7): 1679-1684. doi ...

https://en.wikipedia.org/wiki/Edwin_Southern

Antisense oligonucleotides[edit]. Gene silencing can be achieved by introducing into cells a short "antisense oligonucleotide" ... If the antisense oligonucleotide contains a stretch of DNA or a DNA mimic (phosphorothioate DNA, 2′F-ANA, or others) it can ... Antisense RNA[edit]. Main article: Antisense RNA. An RNA sequence that is complementary to an endogenous mRNA transcript is ... In recent years, some alternative antisense structural types have been experimentally applied as antisense therapy.[citation ...

https://en.wikipedia.org/wiki/Sense_

Higuchi M, Yamayoshi A, Kobori A, Yamaoka T, Murakami A: Synthesis and properties of photo-reactive antisense oligonucleotides ...

https://sh.wikipedia.org/wiki/Trioksalen

... using in particular anti-sense oligonucleotides.[44] The movement disorders associated with ataxia can be managed by ...

https://en.wikipedia.org/wiki/Ataxia

Efficient stimulation of site-specific ribosome frameshifting by antisense oligonucleotides. , journal = RNA , volume = 10 , ...

https://gl.m.wikipedia.org/wiki/Especial:MobileDiff/4969671

... s, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a ... "Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly augmented by antisense molecules targeted to ... single-stranded oligonucleotides which contain a single ribonucleotide base to act as the cleavage site. Once sequenced, this ... which shows how oligonucleotides undergo competitive binding with the targets and how the evolutionary outcome can be improved ...

https://en.wikipedia.org/wiki/Deoxyribozyme

LCR can be used to diagnose tuberculosis.[17] The sequence containing protein antigen B is targeted by four oligonucleotide ... primers-two for the sense strand, and two for the antisense strand. The primers bind adjacent to one another, forming a segment ...

https://en.wikipedia.org/wiki/Amplicon

For antisense oligomer delivery[edit]. Antisense oligonucleotides (asONs) have been used in basic research and are being ... Nucleic acid-based macromolecules such as siRNA, antisense oligonucleotide, decoy DNA, and plasmid have been realized as ... Eckstein, Fritz (2007). "The versatility of oligonucleotides as potential therapeutics". Expert Opinion on Biological Therapy. ... CPP strategies have been developed to deliver antisense oligomers such as PNA and PMO into cells. Overcoming the repulsion by ...

https://en.wikipedia.org/wiki/Cell_penetrating_peptide

Synthesis of acyclic oligonucleotides as antiviral and antiinflammatory agents and inhibitors of phospholipase A2. PCT Int. ... Antisense *Processual *Small nuclear *Small nucleolar *Small Cajal Body RNAs. *Y RNA ...

https://en.wikipedia.org/wiki/GNA_

... "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both ... Verma S, Eckstein F (1998). "Modified oligonucleotides: synthesis and strategy for users". Annual Review of Biochemistry. 67: ... Sense and antisense. Further information: Sense (molecular biology). A DNA sequence is called a "sense" sequence if it is the ... Munroe SH (November 2004). "Diversity of antisense regulation in eukaryotes: multiple mechanisms, emerging patterns". Journal ...

https://en.wikipedia.org/wiki/Dna

"Nuclear antisense effects of neutral, anionic and cationic oligonucleotide analogs". Nucleic Acids Research. 29 (19): 3965-74 ... Splicing events can be experimentally altered[34][35] by binding steric-blocking antisense oligos such as Morpholinos or ...

https://en.wikipedia.org/wiki/Splicing_

... urutan RNA antisense juga diproduksi, namun fungsi RNA antisense ini tidaklah diketahui dengan jelas.[33] RNA antisense ... Verma S, Eckstein F (1998). "Modified oligonucleotides: synthesis and strategy for users". Annu. Rev. Biochem. 67: 99-134. doi: ... "antisense". Baik urutan sense dan antisense dapat ditemukan pada berbagai bagian unting DNA yang sama (kedua unting DNA dapat ... Sense dan antisenseSunting. Info lebih lanjut: Sense. Sebuah urutan sekuens DNA disebut sebagai "sense" apabila urutan basa DNA ...

https://id.m.wikipedia.org/wiki/DNA

The oligonucleotides alternate between sense and antisense directions, and the overlapping segments determine the order of the ... PCR employs two main reagents - primers (which are short single strand DNA fragments known as oligonucleotides that are a ... ends of each of the sense and anti-sense strands of the DNA target (DNA polymerase can only bind to and elongate from a double- ... artificial synthesis of long DNA sequences by performing PCR on a pool of long oligonucleotides with short overlapping segments ...

https://en.m.wikipedia.org/wiki/Polymerase_chain_reaction

... for example by using antisense oligonucleotides targeting specific mRNA molecules. DNA oligonucleotides complementary to ... "Defining synphenotype groups in Xenopus tropicalis by use of antisense morpholino oligonucleotides". PLOS Genet. 2 (11): e193. ... the use of morpholino-antisense oligonucleotides for gene knockdowns in vertebrate embryos, which is now widely used, was first ... Morpholino oligonucleotidesEdit. Main article: Morpholino. Morpholino oligos are used in both X. laevis and X. tropicalis to ...

https://en.m.wikipedia.org/wiki/Xenopus

C. Frank Bennett, Ionis Pharmaceuticals, Carlsbad, the development of an effective antisense oligonucleotide therapy for ... and for establishing antisense oligonucleotide therapy in animal models of ALS and Huntington disease. ... for the development of an effective antisense oligonucleotide therapy for children with the neurodegenerative disease spinal ...

https://en.wikipedia.org/wiki/Breakthrough_Prize_in_Life_Sciences

Morpholino-type antisense oligonucleotides, with the same cellular target as nusinersen, remain a subject of intense research, ... "Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy". Proceedings of the ... "Repeated low doses of morpholino antisense oligomer: An intermediate mouse model of spinal muscular atrophy to explore the ...

https://en.m.wikipedia.org/wiki/Spinal_muscular_atrophy

Fichou Y, Férec C (2006)։ «The potential of oligonucleotides for therapeutic applications»։ Trends in Biotechnology 24 (12): ... Cavaillé J, Nicoloso M, Bachellerie JP (1996)։ «Targeted ribose methylation of RNA in vivo directed by tailored antisense RNA ... Vater A, Klussmann S (January 2015)։ «Turning mirror-image oligonucleotides into drugs: the evolution of Spiegelmer ...

https://hy.wikipedia.org/wiki/ՌՆԹ

The regions coding miRNA can be independent RNA-genes often being anti-sense to neighboring protein-coding genes, or can be ... This non-protein coding oligonucleotide is itself coded by longer nuclear DNA sequence usually transcribed by RNA polymerase II ... Mätlik K, Redik K, Speek M (2006). "L1 antisense promoter drives tissue-specific transcription of human genes". Journal of ...

https://en.wikipedia.org/wiki/Short_interspersed_nuclear_element

As another strategy for targeting RNA, antisense oligonucleotides were developed which have been pushed forward through the ... While backbone modifications to antisense oligonucleotides in order to prevent nuclease degradation have been shown to work, ... one can identify an RNA involved in disease then the sequence can be used to design a complementary antisense oligonucleotide, ... showed for the first time that small molecules appear to have selectivities that are competitive with oligonucleotides with ...

https://en.wikipedia.org/wiki/RNA-targeting_small_molecule_drugs

"Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides". Nature. 528 (7580): 123- ... Huda Y. Zoghbi, have reversed MECP2 Duplication Syndrome in adult symptomatic mice using antisense therapy. Mice treated with ...

https://en.wikipedia.org/wiki/MECP2_duplication_syndrome

... of human ribonucleases H1 and H2 in the variation of response of cells to antisense phosphorothioate oligonucleotides". Eur. J ... 2004). "Determination of the role of the human RNase H1 in the pharmacology of DNA-like antisense drugs". J. Biol. Chem. 279 ( ...

https://en.wikipedia.org/wiki/RNASEH1

Another independent approach is to use oligoadenylated anti-telomerase antisense oligonucleotides and ribozymes to target ... telomerase RNA, reducing dissociation and apoptosis (Figure 5). The fast induction of apoptosis through antisense binding may ...

https://en.wikipedia.org/wiki/Telomerase

Oligonucleotide phosphorothioates (OPS) are modified oligonucleotides where one of the oxygen atoms in the phosphate moiety is ... Kurreck, J., "Antisense technologies. Improvement through novel chemical modifications", European Journal of Biochemistry 2003 ... They are the basis of antisense therapy, e.g., the drugs fomivirsen (Vitravene), oblimersen, alicaforsen, and mipomersen ( ... Phosphorothioates are the basis for antisense therapies. Amifostine, which is used in cancer chemotherapy. Chlorpyrifos, a ...

https://en.wikipedia.org/wiki/Thiophosphate

... glucocorticoid receptor antisense oligonucleotide for type 2 diabetes mellitus [27] Levoketoconazole (COR-003, NormoCort, ...

https://en.wikipedia.org/wiki/List_of_investigational_hormonal_agents

... biophysical properties and biological activity of second generation antisense oligonucleotides containing chiral ... Because the system uses a plasmid that expresses the exo and gam genes from the λ-red system it is able to use oligonucleotide ... The next step in the no-SCAR protocol is to transform the pCas9cr4 and pKDsg-XXX plasmids and linear oligonucleotides into the ... Transformed oligonucleotides are incorporated into the cellular DNA through λ-red- and Cas9 endonuclease-mediated homologous ...

https://en.wikipedia.org/wiki/No-SCAR_(Scarless_Cas9_Assisted_Recombineering)_Genome_Editing

He has been involved in the development of antisense oligonucleotides as therapeutic agents, including research on the ... oligonucleotide delivery, pharmacokinetics and medicinal chemistry. Notably, Bennett led the development of antisense ... Krainer for the development of an effective antisense oligonucleotide therapy for children with the neurodegenerative disease ... Bennett has published more than 200 papers on antisense technology and has more than 175 issued U.S. Patents. Bennett was the ...

https://en.wikipedia.org/wiki/C._Frank_Bennett

Antisense Oligonucleotides. Class Summary. Antisense oligonucleotides (ASO) designed to treat SMA caused by mutations in ...

https://emedicine.medscape.com/article/1181436-medication

In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically ... The oligonucleotide comprises nucleotide units sufficient in identity and number to effect said specific hybridization. In ... In additional preferred embodiments, the oligonucleotides are specifically hybridizable with RNA sequences involved in splicing ... other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a ...

http://www.google.com/patents/US5580767?dq=5,815,488

Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons.. Kirsch J1, Wolters I, Triller A, ... Here we report that treatment of rat spinal neurons in culture with gephyrin antisense oligonucleotides prevents the formation ...

https://www.ncbi.nlm.nih.gov/pubmed/8264797?dopt=Abstract

This Perspective describes a promising approach to RNA repair based on the use of antisense oligonucleotides to modulate ... Modification of splicing by antisense oligonucleotides. Aberrant splicing in thalassemic β-globin pre-mRNA or in certain splice ... Similarly, oligonucleotides induce skipping of a normal exon (gray) (. b. ) or force selection of an alternative 5′ splice site ... mutants in CFTR is prevented, and correct splicing is restored, by oligonucleotides (dark red bars) that block aberrant 5′ or 3 ...

https://www.jci.org/articles/view/19547/figure/1

Two different antisense oligonucleotide-based (ASO-based) therapies are currently in clinical use to treat neuromuscular ...

https://www.jci.org/articles/view/131933/pdf

Two different antisense oligonucleotide-based (ASO-based) therapies are currently in clinical use to treat neuromuscular ... Better living through peptide-conjugated chemistry: next-generation antisense oligonucleotides. Elizabeth M. McNally and Brian ...

https://jci.org/articles/view/131933/pdf

Bio-Synthesiss BNA gapmers chimeric antisense RNA oligonucleotide give you the highest knock-down, lowest off-target effect ... RNase H-Active Antisense Oligonucleotide Services. Gapmer antisense chimeras are designed to have both 2OMe RNA and BNA in the ... In antisense technology, a single-stranded oligonucleotide added from outside may bind with target mRNA to form oligonucleotide ... BNA gapmer antisense RNA oligonucleotides offer greater potency and low toxicity than other modified nucleotide. ...

http://www.biosyn.com/bna-gapmer-antisense-rna-oligonucleotide.aspx

Antisense oligonucleotides directed at the bcl-xl gene product engender apoptosis in mesothelioma cell lines. The therapeutic ... Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product J Thorac Cardiovasc Surg. ... Conclusion: Antisense oligonucleotides directed at the bcl-xl gene product engender apoptosis in mesothelioma cell lines. The ... Results: Bcl-xl protein expression after antisense oligonucleotides was downwardly regulated in both cell lines relative to ...

https://pubmed.ncbi.nlm.nih.gov/12063468/?dopt=Abstract

... oligonucleotides antisense include Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System. ... Oligonucleotides, Antisense: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which ...

https://www.jove.com/keyword/oligonucleotides+antisense

Delivery of Oligonucleotides to Cells. In order for an antisense oligonucleotide to down-regulate gene expression, it must ... Efficiency of Antisense Oligonucleotides. In practice, only a few complementary oligonucleotides can successfully hybridize to ... Regulation of in vitro gene expression using antisense oligonucleotides or antisense expression plasmids transfected using ... Antisense morpholino oligonucleotide analog induces missplicing of C-myc mRNA. Antisense Nucleic Acid Drug Dev., 9: 213 -220, ...

https://mct.aacrjournals.org/content/1/5/347.full

With the recent approvals of two antisense oligonucleotides for the treatment of the genetic diseases Duchenne muscular ... Consideration is given to the advantages antisense oligonucleotides would have as an anti-fibrotic therapy alongside factors ... A prospective outlook for the development of antisense oligonucleotides to target fibrosis is outlined. ... we explore here the potential of antisense oligonucleotides to knockdown the expression of pro-fibrotic proteins. We give an ...

https://www.mdpi.com/2227-9059/6/3/74

T. Koo and M. Wood, "Clinical trials using antisense oligonucleotides in duchenne muscular dystrophy," Human Gene Therapy, vol ... N. Dias and C. A. Stein, "Antisense oligonucleotides: basic concepts and mechanisms," Molecular Cancer Therapeutics, vol. 1, no ... T. Yokota, S. Takeda, Q.-L. Lu, T. A. Partridge, A. Nakamura, and E. P. Hoffman, "A renaissance for antisense oligonucleotide ... O-methyl-phosphorothioate RNA antisense oligonucleotides in the mdx mouse model," Molecular Therapy, vol. 18, no. 6, pp. 1210- ...

https://www.hindawi.com/journals/bmri/2013/402369/ref/

The use of antisense oligonucleotide (man-made molecules; ASO) aims to induce a long-term decrease in expression of this ... The use of antisense oligonucleotide (man-made molecules; ASO) aims to induce a long-term decrease in expression of this ...

https://www.michaeljfox.org/grant/novel-lrrk2-antisense-oligonucleotides-therapy-parkinsons-disease

Here we explore methods for the peptide-mediated delivery of antisense oligonucleotides (ASOs) and chemotherapeutics. First, we ... Peptide-mediated delivery of antisense oligonucleotides and chemotherapeutics across biological barriers. Research and Teaching ... Peptide-mediated delivery of antisense oligonucleotides and chemotherapeutics across biological barriers. Download ...

http://dspace.mit.edu/handle/1721.1/118259

... providing a platform for preclinical evaluation of multi-exon antisense therapy. ...

https://dmm.biologists.org/keyword/antisense-oligonucleotide

Treatment of primary cynomolgus hepatocytes with a PTP-1B antisense oligonucleotide, ISIS 113715, reduces PTP-1B mRNA and ... Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases ... Inhibition of Protein Tyrosine Phosphatase-1B with Antisense Oligonucleotides Improves Insulin Sensitivity and Increases ... Inhibition of Protein Tyrosine Phosphatase-1B with Antisense Oligonucleotides Improves Insulin Sensitivity and Increases ...

https://www.ncbi.nlm.nih.gov/pubmed/19164474?dopt=Abstract

There is great interest in therapeutic oligonucleotides (ONs), such as siRNA and antisense oligonucleotides (ASOs), for ... Dendrimer conjugates for light-activated delivery of antisense oligonucleotides†. Ahu Yuanab, Yiqiao Hub and Xin Ming*a a ... M. R. Alam, X. Ming, V. Dixit, M. Fisher, X. Chen and R. L. Juliano, Oligonucleotides, 2010, 20, 103-109 CrossRef CAS PubMed . ... Splice switching oligonucleotide. Acknowledgements. This work was supported by NIH grants 5U54CA151652 and 5R01CA151964 and an ...

https://pubs.rsc.org/en/content/articlehtml/2015/ra/c5ra04091d

Suitable antisense oligonucleotides have a length of from 12 to 35 oligonucleotides and have sequence specificity to the hsp27 ... The oligonucleotides employed as antisense or RNAi molecules may be modified to increase the stability of the oligonucleotides ... Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use. 1995-05-23. Tari et al.. ... The amount of antisense oligonucleotide or other therapeutic administered is one effective to reduce the amount of active hsp ...

http://www.freepatentsonline.com/9381209.html

i,Aim.,/i, To assess the efficiency of phosphorothioate antisense oligodeoxynucleotide 1 (S-ODN1) on HCV translation inhibition ... In Vitro Inhibition of Hepatitis C Virus by Antisense Oligonucleotides in PBMC Compared to Hepatoma Cells,. BioMed Research ... M. K. El-Awady, N. G. B. El-Din, W. T. El-Garf et al., "Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 ... R. Hanecak, V. Brown-Driver, M. C. Fox et al., "Antisense oligonucleotide inhibition of hepatitis C virus gene expression in ...

https://www.hindawi.com/journals/bmri/2014/196712/

Antisense oligonucleotides have been investigated as potential drugs for years. They inhibit target gene or protein expression ... antisense oligonucleotides with the use of mass spectrometry.". Antisense oligonucleotides have been investigated as potential ... Antisense therapy with the use of antisense oligonucleotides (AON) ha.... Extending Urine Analysis By Direct Mass Spectrometry ... Home » Topics » Antisense therapy » Research » Review on investigations of antisense oligonucleotides with the use of mass ...

https://www.bioportfolio.com/resources/pmarticle/1845669/Review-on-investigations-of-antisense-oligonucleotides-with-the-use-of-mass-spectrometry.html

Exon skipping uses antisense oligonucleotides (ASOs) to alter transcript splicing for the purpose of rescuing or modulating ... Welcome to the splice age: antisense oligonucleotide-mediated exon skipping gains wider applicability. ... Welcome to the splice age: antisense oligonucleotide-mediated exon skipping gains wider applicability. ...

https://jci.org/articles/view/86799/figure/1

Wrangling RNA: Antisense oligonucleotides for neurological disorders Message Subject. (Your Name) has forwarded a page to you ... Effective treatment of spinal muscular atrophy with antisense oligonucleotide therapy opens the door to treating other ... Effective treatment of spinal muscular atrophy with antisense oligonucleotide therapy opens the door to treating other ... Development of next-generation ASO compounds will arise from advances in oligonucleotide chemistry, including stereoselective ...

https://stm.sciencemag.org/content/11/511/eaay2069/tab-figures-data

... modified antisense oligonucleotides in animals and man. In Antisense Drug Technology: Principles, Strategies, and Applications ... Antisense oligonucleotides (ASOs) provide a specific and rapid method for lowering target gene expression. ASOs are well ... Suppression of choroid plexus transthyretin levels by antisense oligonucleotide treatment. Amyloid 2010;17:43-49pmid:20462362. ... PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic ...

https://diabetes.diabetesjournals.org/content/64/5/1603

Antisense oligonucleotides (AOs) can be used to redirect dystrophin pre-messenger RNA (mRNA) processing, to remove selected ... The influence of antisense oligonucleotide length on dystrophin exon skipping Mol Ther. 2007 Jan;15(1):157-66. doi: 10.1038/sj. ... Antisense oligonucleotides (AOs) can be used to redirect dystrophin pre-messenger RNA (mRNA) processing, to remove selected ...

https://pubmed.ncbi.nlm.nih.gov/17164787/?dopt=Abstract

Treatment of diet-induce obese (DIO) mice with FGFR4 antisense oligonucleotides (ASO) specifically reduced liver FGFR4 ... Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious ... Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4) in peripheral ...

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066923

... gene therapy and antisense oligonucleotides as potential treatments for autism spectrum disorders. The panel discussion will be ... genes and antisense oligonucleotides: Industry perspectives on treatment development for ASD on SFARI ... Small molecules, genes and antisense oligonucleotides: Industry perspectives on treatment development for ASD ... Small molecules, genes and antisense oligonucleotides: Industry perspectives on treatment development for ASD. ...

https://www.sfari.org/event/small-molecules-genes-and-antisense-oligonucleotides-industry-perspectives-on-treatment-development-for-asd/

What is Oligonucleotides, antisense? Meaning of Oligonucleotides, antisense medical term. What does Oligonucleotides, antisense ... antisense in the Medical Dictionary? Oligonucleotides, antisense explanation free. ... oligonucleotide. (redirected from Oligonucleotides, antisense). Also found in: Dictionary, Encyclopedia. oligonucleotide. [ol″ĭ ... Oligonucleotides, antisense , definition of Oligonucleotides, antisense by Medical dictionary https://medical-dictionary. ...

https://medical-dictionary.thefreedictionary.com/Oligonucleotides%2C+antisense

... charge density has clear potential for exploration towards achieving higher efficiency of antisense oligonucleotide systemic ... and their antisense effect and toxicity were evaluated both in vitro and in mdx mice. The results showed that the exon-skipping ... antisense oligonucleotide; muscular dystrophy amphiphilic peptide; exon-skipping; antisense oligonucleotide; muscular dystrophy ... Evaluation of Amphiphilic Peptide Modified Antisense Morpholino Oligonucleotides In Vitro and in Dystrophic mdx Mice by ...

https://www.mdpi.com/2073-4360/9/5/177

2007) Antisense Oligonucleotide. In: Schmidt R., Willis W. (eds) Encyclopedia of Pain. Springer, Berlin, Heidelberg. * .RIS ...

https://rd.springer.com/referenceworkentry/10.1007/978-3-540-29805-2_261

Antisense phosphorothioate oligonucleotides that downregulate the cellular expression of human ENT1 nucleoside transporter. ... Antisense phosphorothioate oligonucleotides that downregulate the cellular expression of human ENT1 nucleoside transporter ... Antisense phosphorothioate oligonucleotides that downregulate the cellular expression of human ENT1 nucleoside transporter ... Antisense phosphorothioate oligonucleotides that downregulate the cellular expression of human ENT1 nucleoside transporter ...

http://cancerres.aacrjournals.org/content/65/9_Supplement/1286.3

Here we explore methods for the peptide-mediated delivery of antisense oligonucleotides (ASOs) and chemotherapeutics. (mit.edu)
however, treatment of rodents with antisense oligonucleotides (ASOs) directed against PTP-1B improves insulin sensitivity, inhibits lipogenic gene expression, and reduces triglyceride accumulation in liver and adipose tissue. (nih.gov)
There is great interest in therapeutic oligonucleotides (ONs), such as siRNA and antisense oligonucleotides (ASOs), for treating various diseases. (rsc.org)
Antisense oligonucleotides (ASOs) are synthetic bioactive compounds used as therapeutic agents in clinical trials. (bioportfolio.com)
Exon skipping uses antisense oligonucleotides (ASOs) to alter transcript splicing for the purpose of rescuing or modulating protein expression. (jci.org)
Since lowering TTR levels increases renal clearance of RBP4, we determined whether decreasing TTR levels with antisense oligonucleotides (ASOs) improves glucose metabolism and insulin sensitivity in obesity. (diabetesjournals.org)
In this panel, industry leaders Federico Bolognani, Stuart Cobb and Yael Weiss provided their perspectives on three different treatment approaches that are currently being pursued for ASD and related conditions: small molecules, gene therapies and antisense oligonucleotides (ASOs). (sfari.org)
Splicing modulators such as antisense oligonucleotides (ASOs) therefore come to the forefront of therapeutic candidates. (pnas.org)
Using this new model, in combination with clinical electrophysiology methods, we found that administering systemically SMN-restoring antisense oligonucleotides (ASOs) at the age of onset can extend survival and rescue the neurological phenotypes. (pnas.org)
Antisense Oligonucleotides (ASOs) are an emerging field of gene therapeutics. (unl.edu)
In the present study, we used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. (diabetesjournals.org)
Antisense oligonucleotides (ASOs) may offer advantages over traditional therapies if an appropriate target can be identified. (cancer.gov)
Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression. (urotoday.com)
Antisense oligonucleotides (ASOs) based therapy is a promising strategy for combating Multi-Drug Resistant (MDR) bacteria because of its high specificity, easy design and lower induction of resistance, but poor cellular uptake by bacteria has restricted the further utilization of this therapy. (eurekaselect.com)
Munich/Martinsried, Germany, January 20, 2020 - Secarna Pharmaceuticals GmbH & Co. KG ("Secarna"), a biopharmaceutical company focusing on the discovery and development of next generation antisense oligonucleotide (ASO) therapies to address challenging or previously undruggable targets via its LNAplus TM platform, today announced the publication of data on the role of bioinformatic screening in the process of generating and selecting ASOs. (pharmiweb.com)
For discovering, testing and selecting antisense oligonucleotides (ASOs) for pre-clinical and clinical development, Secarna employs its proprietary, customized LNAplus TM drug discovery platform. (pharmiweb.com)
Antisense oligonucleotides (ASOs) have proven successful in treating children with spinal muscular atrophy, a severe infantile neurological disorder, and several ASOs are currently being tested in clinical trials for various neurological disorders. (ovid.com)
Antisense oligonucleotides (ASOs) are DNA-based, disease-modifying drugs. (onmedica.com)
The use of antisense oligonucleotides (ASOs) as a platform for drug development to treat these diseases has increased significantly over the years due to their unique mechanism of action at the RNA level ( Bennett and Swayze, 2010 ). (aspetjournals.org)
We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. (bioscirep.org)
Therapeutic inhibition of AGT mRNA expression using antisense oligonucleotides (ASOs) obviates developmental issues caused by genetic manipulations of AGT, thereby providing opportunities to more precisely determine roles of AGT in hypertension and many other diseases. (bioscirep.org)
Antisense oligonucleotides (ASOs) are 15-25 nt oligonucleotides designed to tie complementary RNA targets for the degradation. (marketresearchreports.biz)
Antisense oligonucleotides (ASOs) are being developed as treatments for rare genetic disorders such as SCN2A. (scn2aaustralia.org)
Antisense oligonucleotides (ASOs) are a single-stranded DNA or RNA sequence consisting of 15-25 nucleotides paired with a target gene. (synbio-tech.com)
However, the drug ASOs usually have specific modifying groups to enhance the stability of oligonucleotides in vivo , improve their specificity, and reduce their toxic side effects. (synbio-tech.com)
Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). (wikipedia.org)

Bio-Synthesis's BNA gapmers chimeric antisense RNA oligonucleotide technology gives you the highest knock-down, lowest off-target effect to achieve efficient inhibition of coding and non coding long RNAs (lncRNAs). (biosyn.com)
We have previously shown pharmacologic inhibition of bcl-xl expression in malignant pleural mesothelioma can lead to apoptosis, so we sought to determine whether antisense oligonucleotides directed at bcl-xl messenger RNA would engender apoptosis, possibly through a "forced imbalance" of bcl-2 family proteins. (nih.gov)
Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases adiponectin concentrations. (nih.gov)
To assess the efficiency of phosphorothioate antisense oligodeoxynucleotide 1 (S-ODN1) on HCV translation inhibition in PBMC compared to hepatoma cells in vitro for the first time. (hindawi.com)
We have previously shown that antisense inhibition of BCL-XL in MPM cells leads to apoptosis. (aacrjournals.org)
Cotten M, Schaffner G, Birnstiel ML (1989) Ribozyme, antisense RNA, and antisense DNA inhibition of U7 small nuclear ribonucleoprotein-mediated histone pre- mRNA processing in vitro. (springer.com)
Moreover, inhibition of FAK gene expression by a phosphorothioated antisense oligodeoxynucleotide targeting the portion of the gene encoding amino acids 262-268, increased the sensitivity of ZR-75-1, MDA-MB-231 and MCF7 breast cancer cells to treatment with TPT or CPT-11. (scielo.org.ar)

With the recent approvals of two antisense oligonucleotides for the treatment of the genetic diseases Duchenne muscular dystrophy and spinal muscular atrophy, we explore here the potential of antisense oligonucleotides to knockdown the expression of pro-fibrotic proteins. (mdpi.com)
The potential of antisense oligonucleotides to treat neurodegenerative diseases was reviewed by Tabrizi in Science in 2020. (wikipedia.org)

In this study, the effects of administration of antisense oligonucleotides to gastrin on growth of pancreatic cancer were evaluated in vitro and in vivo. (elsevier.com)

Effective treatment of spinal muscular atrophy with antisense oligonucleotide therapy opens the door to treating other neurological disorders with this approach. (sciencemag.org)
In 2004, development of an antisense therapy for spinal muscular atrophy began. (wikipedia.org)

3. A method of inhibiting influenza virus replication in cells in vitro by introducing an oligonucleotide having SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 or SEQ ID NO: 8, wherein at least some of the internucleotide linkages within said oligonucleotide are phosphorothioate linkages, into said cells in an amount sufficient to inhibit replication. (google.com)
wherein at least some of the internucleotide linkages within said oligonucleotide are phosphorothioate linkages, into said cells in an amount sufficient to inhibit replication. (google.com)
Do you have the need to find an efficient way to down regulate a targeted protein or inhibit gene function while maintaining strong biostability, superior potency and low toxicity for your antisense therapy? (biosyn.com)
The concept underlying antisense technology is relatively straightforward: the use of a sequence, complementary by virtue of Watson-Crick bp hybridization, to a specific mRNA can inhibit its expression and then induce a blockade in the transfer of genetic information from DNA to protein. (aacrjournals.org)
Antisense 2'-O-methyl oligoribonucleotides were used to block a number of sequences in these pre-mRNAs and were tested for their ability to inhibit splicing in vitro or to affect the ratio between aberrantly and correctly spliced products. (asm.org)
Antisense approaches targeting the epidermal growth factor receptor (EGFR) have been demonstrated to inhibit the growth of squamous cell carcinoma of the head and neck (SCCHN). (aacrjournals.org)
Therapeutic interventions that inhibit c-Myc expression have been extensively investigated, including antisense oligonucleotides that have high specificity and potential clinical application. (garvan.org.au)
Gene therapy with the antisense MT-MMP-1 oligonucleotides might inhibit SMC proliferation and migration in vitro and in vivo. (nii.ac.jp)
PCL20-116: Can Antisense Oligonucleotides Targeted to K-Ras Gene Inhibit the Tumor Growth, Invasiveness and Expression of MMP-2 and MMP-9 In Vitro and In Vivo in Hamster Experimental Pancreatic Cancer Model? (jnccn.org)
Antisense oligonucleotides targeting protein kinase C-alpha, -beta I, or -delta but not -eta inhibit lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages: involvement of a nuclear factor kappa B-dependent mechanism. (semanticscholar.org)

The published abstract entitled, "Phase I Study of LErafAON-ETU, an Easy-To-Use Formulation of Liposome Entrapped c-raf Antisense Oligonucleotide, in Advanced Cancer Patients," highlights the successful initial clinical dosing of this novel drug formulation. (rxpgnews.com)
abstract = "Antisense oligonucleotides provide attractive possibilities for developing a new class of drugs and the design principle involves straightforward base-pairing rules. (elsevier.com)

In other preferred embodiments, the oligonucleotides are specifically hybridizable with a transcription initiation site, a translation initiation site, 5'-untranslated sequences, 3'-untranslated sequences, and intron/exon junction of influenza virus mRNAs. (google.com)
Similarly, oligonucleotides induce skipping of a normal exon (gray) ( b ) or force selection of an alternative 5′ splice site ( c ) by antisense oligonucleotides targeted to appropriate splice sites. (jci.org)
Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations," Human Mutation , vol. 30, no. 3, pp. 293-299, 2009. (hindawi.com)
Antisense PMO found in dystrophic dog model was effective in cells from exon 7-deleted DMD patient," PLoS ONE , vol. 5, no. 8, Article ID e12239, 2010. (hindawi.com)
Functional analysis of 114 exon-internal AONs for targeted DMD exon skipping: indication for steric hindrance of SR protein binding sites," Oligonucleotides , vol. 15, no. 4, pp. 284-297, 2005. (hindawi.com)
Comparative analysis of antisense oligonucleotide sequences for targeted skipping of exon 51 during dystrophin pre-mRNA splicing in human muscle," Human Gene Therapy , vol. 18, no. 9, pp. 798-810, 2007. (hindawi.com)
Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells," Human Molecular Genetics , vol. 10, no. 15, pp. 1547-1554, 2001. (hindawi.com)
The most common SGCG mutation that causes LGMD 2C has been modeled in mice using gene editing, providing a platform for preclinical evaluation of multi-exon antisense therapy. (biologists.org)
Identification and characterization by antisense oligonucleotides of exon and intron sequences required for splicing. (asm.org)
and (iii) improving the 5' splice site of the internal exon to match the consensus sequence strongly decreases the accessibility of the upstream 3' splice site to antisense 2'-O-methyl oligoribonucleotides. (asm.org)

Consideration is given to the advantages antisense oligonucleotides would have as an anti-fibrotic therapy alongside factors that would need to be addressed to improve efficacy. (mdpi.com)
Consequently, antisense technologies are still needed in the future therapy for HCV. (hindawi.com)
Antisense therapy with the use of antisense oligonucleotides (AON) ha. (bioportfolio.com)
On May 14, 2021, Federico Bolognani, Stuart Cobb, and Yael Weiss joined a panel to discuss new industry developments on the use of small molecules, gene therapy and antisense oligonucleotides as treatment approaches for autism spectrum disorders (ASD). (sfari.org)
A novel therapy by Genta Inc called Genasense is a oligonucleotide that targets and destroys the message RNA for Bcl-2, the anti-apoptotic protien that drives this leukemia. (oncolink.org)
have turned to genetic technology, demonstrating an antisense oligonucleotide-based therapy for inhibiting KRAS . (sciencemag.org)
A potential application of molecular therapy with antisense oligonucleotides is the prevention or treatment of restenosis after coronary interventions (1,2) . (onlinejacc.org)
Antisense oligonucleotides have been widely used in gene therapy due to their advantages of high specificity, high efficiency, and low toxicity. (synbio-tech.com)

Secarna Pharmaceuticals is the next generation antisense oligonucleotide (ASO) company addressing high unmet medical needs in the areas of immuno-oncology, immunology, as well as viral, neurodegenerative and cardiometabolic diseases. (pharmiweb.com)

We report the first-in-human dose study of LY2181308, a second-generation antisense oligonucleotide (ASO) directed against survivin mRNA. (semanticscholar.org)

Moreover, significant advances in the field of antisense oligonucleotides at a therapeutic or clinical level is further contributing to the growth of the global antisense oligonucleotides market. (marketresearchreports.biz)

In particular, this invention relates to antisense oligonucleotide interactions with certain viral ribonucleic acids and messenger ribonucleic acids involved in the infection of cells by influenza viruses. (google.com)
The invention relates to antisense oligonucleotides to proto-oncogenes, and in particular to antisense oligo¬ nucleotides to the c-myb gene, and the use of such oligo¬ nucleotides as antineoplastic and immunosuppressive agents. (google.com)

The role of stannin in mediating TMT toxicity in primary cultures was investigated by blocking stannin expression with specific antisense oligonucleotides. (aspetjournals.org)
The MOE modification has led to the development of potent, pharmacologically active, specific antisense oligonucleotides, one of which is ISIS 301012. (aspetjournals.org)

McNally, EM & Leverson, BD 2019, ' Better living through peptide-conjugated chemistry: Next-generation antisense oligonucleotides ', Journal of Clinical Investigation , vol. 129, no. 11, pp. 4570-4571. (northwestern.edu)
In 2019, a report was published detailing the development of milasen, an antisense oligonucleotide drug for Batten disease, under an expanded-access investigational clinical protocol authorized by the Food and Drug Administration (FDA). (wikipedia.org)

1 and 2 ), and to numerous clinical trials of therapeutic oligonucleotides ( 3 ). (aacrjournals.org)
Therapeutic oligonucleotides (ONs), such as splice switching ONs (SSOs), provide opportunities for treating serious, life-threatening diseases. (rsc.org)
Finally, certain conclusions and perspectives on the determination of therapeutic oligonucleotides in various samples were briefly described. (bioportfolio.com)
Therapeutic oligonucleotides: a review. (synbio-tech.com)

Becker D, Meier CB, Herlyn M (1989) Proliferation of human malignant melanomas is inhibited by antisense oligodeoxynucleotides targeted against basic fibroblast growth factor. (springer.com)
In order to explore the importance of c-Fos and JunB, the predominantly expressed AP-1 proteins for the phase-shifting effects of light, we blocked the expression of c-Fos and JunB in the suprachiasmatic nucleus of male rats, housed under constant darkness, by intracerebroventricular application of 2 microliters of 1 mM antisense phosphorothioate oligodeoxynucleotides (ASO) specifically directed against c-fos and junB mRNA. (biomedsearch.com)
We analyzed their role in tumor-cell proliferation in 12 glioma cell lines, employing phosphorothioate antisense oligodeoxynucleotides (S-ODNs, 14 mer), specifically targeted against the coding sequences of TGF-beta 1-mRNA and TGF-beta 2-mRNA. (uni-regensburg.de)
There have been 2 methods of delivering antisense: one is by oligodeoxynucleotides, and the other is with full-length DNA in viral vectors. (ahajournals.org)
We conclude that there is sufficient preclinical data to give serious consideration to phase I trials for testing some of the antisense oligodeoxynucleotides, although testing the viral vectors needs much more work. (ahajournals.org)

Two different antisense oligonucleotide-based (ASO-based) therapies are currently in clinical use to treat neuromuscular diseases. (jci.org)
LNAplus TM encompasses all aspects of drug discovery and pre-clinical development and has proven to be fast, reliable, scalable, efficient and to provide for a uniquely integrated workflow, enabling the discovery of novel antisense-based therapies for challenging or currently undruggable targets. (pharmiweb.com)
Secarna's mission is to maximize the performance and output of its proprietary LNAplus TM antisense oligonucleotide discovery platform, as well as to develop highly specific, safe, and efficacious best-in-class antisense therapies for challenging or currently undruggable targets. (pharmiweb.com)
It is easy to scale up the commercial scale GMP production of these oligonucleotides compared to other biologic therapies. (marketresearchreports.biz)

A prospective outlook for the development of antisense oligonucleotides to target fibrosis is outlined. (mdpi.com)

Systemic delivery of morpholino oligonucleotide restores dystrophin expression bodywide and improves dystrophic pathology," Nature Medicine , vol. 12, no. 2, pp. 175-177, 2006. (hindawi.com)
Systemic delivery of antisense oligoribonucleotide restorers dystrophin expression in body-wide skeletal muscles," Proceedings of the National Academy of Sciences of the United States of America , vol. 102, no. 1, pp. 198-203, 2005. (hindawi.com)
Bodywide skipping of exons 45-55 in dystrophic mdx52 mice by systemic antisense delivery," Proceedings of the National Academy of Sciences of the United States of America , vol. 109, no. 34, pp. 13763-13768, 2012. (hindawi.com)
These data suggest that with optimization of peptide in component, charge density has clear potential for exploration towards achieving higher efficiency of antisense oligonucleotide systemic delivery, and thus is more applicable for clinical application. (mdpi.com)
The antisense oligonucleotide used in this study was chemically modified, allowing systemic delivery through subcutaneous injection and avoiding the need for a specialized delivery vehicle. (sciencemag.org)
Systemic delivery of recombinant adeno-associated virus with DNA antisense to AT 1 receptors in adult rodents decreases hypertension for up to 6 months. (ahajournals.org)

Specific removal of the nonsense mutation from the mdx dystrophin mRNA using antisense oligonucleotides," Neuromuscular Disorders , vol. 9, no. 5, pp. 330-338, 1999. (hindawi.com)
Antisense oligonucleotides (AOs) can be used to redirect dystrophin pre-messenger RNA (mRNA) processing, to remove selected exons from the mature dystrophin mRNA, to overcome nonsense mutations, and/or restore the reading frame. (nih.gov)
Antisense oligonucleotides alter RNA splicing to exclude the nonsense mutation, while still maintaining the open reading frame to produce a shorter, but partially functional dystrophin protein that should ameliorate the extent of pathology. (edu.au)

Antisense oligonucleotides (ASO) designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency may be considered for treatment. (medscape.com)
Treatment of primary cynomolgus hepatocytes with a PTP-1B antisense oligonucleotide, ISIS 113715, reduces PTP-1B mRNA and protein expression. (nih.gov)
The first goal of this clinical research study is to find the highest safe dose of BP1001, a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS), for patients with Philadelphia Chromosome positive CML, AML, ALL and MDS. (clinicaltrials.gov)
The study drug is an antisense molecule complementary to the messenger RNA (mRNA) code for the cell's expression of the protein Grb-2. (clinicaltrials.gov)
BP1001 is an antisense drug, which means it may help stop cancer cells by blocking the action of a protein that signals cancer cells to divide and increase in number. (mdanderson.org)
Here we show that treatment of rabbit chondrocyes and human chondrosarcoma cells HCS-2/8 by ra-a47 antisense S-oligonucleotides significantly reduced the expression of ra-a47 both at mRNA and protein level. (prohealth.com)
Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). (jci.org)
The effects of the c-myc antisense S-ODN and control S-ODN on c-myc mRNA and protein product levels were analyzed using reverse-transcriptase polymerase chain reaction, immunocytochemistry, and immunoblotting, respectively. (arvojournals.org)
RESULTS: Transient suppression of c-myc mRNA and the c-myc protein product by a c-myc antisense S-ODN (2 to 8 microM) strongly inhibited cell proliferation and GAG synthesis in OF derived from patients with GO and healthy individuals. (arvojournals.org)
The efficacy and specificity of antisense effects was validated by Northern-blot analysis and determination of protein concentrations in culture supernatants (ELISA). (uni-regensburg.de)
WAVE Life Science has designed stereopure oligonucleotides to selectively target the mutant HTT allele to lower the production of mHTT protein while leaving healthy HTT protein relatively intact. (theresecrutchermarin.com)

LErafAON-ETU is NeoPharm's easy-to-use liposomal formulation of an antisense oligonucleotide (AON) complementary to the c-raf mRNA sequence, which mediates tumor cell growth. (rxpgnews.com)
The authors conclude that this supports the previous study that Bcl-2 antisense has anti-tumor activity in CLL even in the absence of other cytotoxic drugs. (oncolink.org)
In this study, the effect of a local treatment of the contralateral eye with tumor necrosis factor-alpha (TNF-α)-antisense-oligonucleotides (ASON) on the HSR was investigated. (egms.de)
Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: a proof-of-concept, first-in-human dose study. (semanticscholar.org)

Moreover, the current approaches and applications of mass spectrometry for quantitative analysis of antisense oligonucleotides and their metabolites as well as their impurities during in vitro and in vivo studies were discussed. (bioportfolio.com)
Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system. (bioportfolio.com)
These results suggest that CD40 antisense ODNs effectively interfere with CD154/CD40 interactions in vivo and, therefore, may provide a novel approach to the treatment of patients with chronic IBD. (bmj.com)
In this study, we investigated the effect of XIAP down-regulation by antisense oligonucleotides (AS ODNs) on human non-small cell lung cancer (NIH-H460) growth in vitro and in vivo . (aacrjournals.org)
In vivo nude mice bearing BxPC-3 xenografts were treated daily for 14 days with a 0.1-ml intratumoral injection of either anti-gastrin (5 μM), the scrambled sequence control phosphorothioate oligonucleotide (5 μM), or buffer. (elsevier.com)
Serial in vivo spectroscopy measurements in mice treated with a C16 fatty acid ligand conjugated antisense (LICA) oligonucleotide reveal a dose-dependent therapeutic response within seven days, confirm a several-week duration of action, and demonstrate a two-fold greater target engagement as compared to the unconjugated parent oligonucleotide. (nature.com)

METHODS: The effects of a 16-mer c-myc antisense phosphorothioate oligodeoxynucleotide (S-ODN) on OF monolayers derived from orbital connective tissue of patients with severe GO (n = 6) and healthy individuals (n = 3) were investigated. (arvojournals.org)

A series of amphiphilic peptides modified PMO (Pt-PMO) were prepared, and their antisense effect and toxicity were evaluated both in vitro and in mdx mice. (mdpi.com)
Compositions of antisense oligonucleotides conjugated to peptides of a plurality of N-methylpyrrolecarboxamides linked by peptide bonds is provided. (google.com)

Leverson, Brian D. / Better living through peptide-conjugated chemistry : Next-generation antisense oligonucleotides . (northwestern.edu)

In our program to develop inhibitors and probes for nucleoside transporters, we have designed and tested several antisense phosphorothioate oligonucleotides (ODNs) for their ability to downregulate the cellular expression of the human es (ENT1) nucleoside transporter. (aacrjournals.org)
After sequencing of the rat CD40 gene, five antisense ODNs were designed, of which one (rAS3) effectively downregulated CD40 expression in rat vascular smooth muscle cells as well as the subsequent changes in gene expression in response to CD40 stimulation. (bmj.com)

We developed a chemically modified 2′- O -(2-methoxy)ethyl antisense oligonucleotide (ISIS 110251) inhibitor of PARP-2 and tested it for efficacy in the interleukin (IL)-10-deficient mouse. (aspetjournals.org)
Volanesorsen (previously known as ISIS 304801) is a 20-nucleotide partially 2′- O -(2-methoxyethyl) (2′-MOE)-modified antisense oligonucleotide (ASO) gapmer, which was recently approved in the European Union as a novel, first-in-class treatment in the reduction of triglyceride levels in patients with familial chylomicronemia syndrome. (aspetjournals.org)
The pharmacokinetics of a 2′- O -(2-methoxyethyl)-modified oligonucleotide, ISIS 301012 [targeting human apolipoprotein B-100 (apoB-100)], was characterized in mouse, rat, monkey, and human. (aspetjournals.org)

In additional preferred embodiments, the oligonucleotides are specifically hybridizable with RNA sequences involved in splicing of the viral RNA, or in viral packaging. (google.com)
Oligonucleotides are also provided which hybridize to certain viral RNA sequences important for RNA splicing or for viral packaging. (google.com)
Here we describe the application of synthetic antisense oligonucleotides designed to target specific sequences of the MYC mRNA (MYCASOs). (aacrjournals.org)

Oligonucleotides are provided having a nucleotide sequence complementary to at least a portion of the mRNA transcript of the human c-myb gene. (google.com)
In the presence of the complementary RNA, antisense phosphorothioates (S-oligos) exerted a biphasic effect on RNase H activity. (aspetjournals.org)
Furthermore, 2'-OMe oligonucleotides show slightly increased affinity towards their complementary mRNA target sequence, thereby forming more stable hybrid duplexes compared to their non-modified DNA or RNA counterparts. (microsynth.com)
LNA containing oligonucleotides offer substantially increased affinity for its complementary strand, compared to traditional DNA or RNA oligonucleotides. (microsynth.com)

Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology. (aspetjournals.org)
The synthesis of phosphorothioate oligonucleotides is often accomplished in the pharmaceutical industry by the sulfurisation of the nucleotide-phosphite using phenylacetyl disulfide (PADS) which has an optimal combination of properties. (hud.ac.uk)

Contact Bio-Synthesis for efficient RNA silencing with BNA gapmers antisense oligonucleotide. (biosyn.com)
Bio-Synthesis recommends that all antisense oligos receive RNase free HPLC purification and that oligos undergo a Na + salt exchange before use in cells or live animals to ensure that salts used in purification are removed. (biosyn.com)
The phosphorothioates are the most widely studied oligonucleotides, because of their nuclease stability (although they are by no means nuclease proof) and relative ease of synthesis. (aacrjournals.org)
Development of next-generation ASO compounds will arise from advances in oligonucleotide chemistry, including stereoselective synthesis, coupled with technologies that solve the challenges of intracellular ASO delivery and delivery across the blood-brain barrier. (sciencemag.org)
Bertrand JR, Imbach JL, Paoletti C, Malvy C (1989) Comparative activity of a- and anomeric oligonucleotides on rabbit P globin synthesis: inhibitory effect of CAP targeted α-oligonucleotides. (springer.com)
Boutorin AS, Gusvkova LV, Ivanova EM, Kobetz ND, Zarytova VF, Ryte AS, Yurchenko LV, Vlassov VV (1989) Synthesis of alkylating oligonucleotide derivatives containing cholesterol or phenazinium residues at their 3'-terminus and their interaction within mammalian cells. (springer.com)
These effects were not a result of TNFalpha upregulation, since the ra-a47 antisense oligonucleotide treatment did not enhance TNFalpha synthesis. (prohealth.com)
To determine, using antisense technology, whether the c-myc protooncogene is involved in cell proliferation and glycosaminoglycan (GAG) synthesis in cultured orbital fibroblasts (OF). (arvojournals.org)

Significant cellular killing in both the I-45 and REN cell lines was achieved with antisense oligonucleotides (compared with sense oligonucleotides) without (P =.003 and.006, respectively) and with (P =.006 and.0005, respectively) liposomal delivery. (nih.gov)
Use of a liposomal delivery system increased therapeutic effect and allowed lower doses of antisense oligonucleotides. (nih.gov)

Conceptual simplicity, the possibility of rational design, relatively inexpensive cost, and developments in the sequencing of human genome have led to the use of short fragments of nucleic acid, commonly called oligonucleotides, either as therapeutic agents or as tools to study gene function. (aacrjournals.org)
ISTH0036 is a 14-mer phosphorothiate locked nucleic acid-modified antisense oligonucleotide targeting TGF-β2 mRNA, and was shown to have potent anti-vascular leakage, anti-angiogenic and anti-fibrotic effects in prior studies. (arvojournals.org)
The Journal is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center and Annemieke Aartsma-Rus, PhD, Leiden University Medical Center, and Executive Editor Graham C. Parker, PhD. Nucleic Acid Therapeutics is the official journal of the Oligonucleotide Therapeutics Society. (miragenews.com)
The expertise and resources that Roche is bringing to the collaboration will help us to potentially address one of the biggest challenges in oligonucleotide-based therapeutic development: oral administration of nucleic acids. (medicalnewser.com)

If known genes are being targeted in different cell types, a useful strategy is to search antisense oligo databases, such as that from the University of Utah (http antisense. (rrnursingschool.biz)

Wang M, Wu B, Lu P, Shah SN, Tucker JD, Bollinger LE, Lu Q. Evaluation of Amphiphilic Peptide Modified Antisense Morpholino Oligonucleotides In Vitro and in Dystrophic mdx Mice. (mdpi.com)
The present study investigated the benefits of chronic treatment of mdx mice by oncemonthly deep intramuscular injections of antisense oligonucleotides into paraspinal muscles. (edu.au)
Targeted delivery of antisense oligonucleotides tohepatocytes using triantennary N-acetylgalactosamine improves potency 10-fold in mice. (synbio-tech.com)

In all of the neuronal populations studied here (hippocampal neurons, sympathetic neurons, and PC12 cells), cell death was blocked by the broad spectrum caspase inhibitor N -benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone and more specifically by the downregulation of caspase-2 with antisense oligonucleotides. (jneurosci.org)

We give an overview of the generalized fibrotic process, concentrating on key players and highlight where antisense oligonucleotides have been used effectively in cellular and animal models of different fibrotic conditions. (mdpi.com)
Modulation of cellular functions in retroorbital fibroblasts using antisense oligonucleotides targeting the c-myc protooncogene. (arvojournals.org)
Log phase BxPC-3 human pancreatic cancer cells in culture were exposed to increasing concentrations (0.5-10 μM) of a synthetic 20-mer antisense phosphorothioate oligonucleotide to gastrin for 48 h and growth was assessed by the cellular proliferation assay. (elsevier.com)

As of 2020 more than 50 antisense oligonucleotides were in clinical trials, including over 25 in advanced clinical trials (phase II or III). (wikipedia.org)

However, the intracellular delivery and silencing activity of these oligonucleotides remains a challenge, and depend on the use of transfection agents and delivery systems. (urotoday.com)
Furthermore, the chemistries and delivery strategies of antisense oligonucleotides will be discussed. (eurekaselect.com)
Objectives We evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. (onlinejacc.org)
Conclusions This study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing. (onlinejacc.org)
However, the global antisense oligonucleotides market is grappling with numerous challenges related to diversity of oligonucleotides, delivery, and regulatory complexity. (marketresearchreports.biz)
Conjugation of N-acetylgalactosamine (GalNAc) has become a major clinical strategy for delivery of oligonucleotides to hepatocytes (liver cells). (microsynth.com)

An antisense oligonucleotide (ASO) is a single-stranded, synthetic RNA (or DNA) sequence. (nih.gov)
In antisense technology short synthetic oligonucleotides are supposed to hybridize to a certain sequence of the mRNA (drug target) thereby interfering with the mRNA processing. (microsynth.com)

Antisense oligonucleotide to gastrin may have a role in the future treatment of patients with pancreatic cancer. (elsevier.com)

Oligonucleotide Therapeutics Society c/o Event Innovations, Inc. (oligotherapeutics.org)

Block of c-Fos and JunB expression by antisense oligonucleotides inhibits light-induced phase shifts of the mammalian circadian clock. (biomedsearch.com)
We explored membrane-type matrix metalloproteinase- 1 (MT-MMP- 1) gene expressions in balloon-injured rat carotid artery, and that whether antisense MT-MMP-1 oligonucleotide inhibits cultured smooth muscle cell (SMC) proliferation and migration. (nii.ac.jp)

Together, these results suggest that the non-sequence-specific inhibitory effect of S-oligos should be taken into consideration in designing antisense inhibitors. (aspetjournals.org)
This inhibitory activity could be avoided by decreasing the number of phosphorothioate linkages at the backbone, and S-oligos of 15-20 residues are preferable in antisense molecule design. (aspetjournals.org)

However, although antisense oligonucleotides are commonly in use now both in the laboratory and clinic, this theoretical simplicity belies the many questions concerning the molecular mechanisms of action of these compounds. (aacrjournals.org)
Oligonucleotides incorporating 2'-O-methoxyethyl (MOE)-modified nucleotides, can support most, if not all antisense mechanisms of action. (microsynth.com)

Here we report that treatment of rat spinal neurons in culture with gephyrin antisense oligonucleotides prevents the formation of GlyR clusters in the dendritic plasma membrane. (nih.gov)
Phosphorothioate modified ODN (S-ODN) is the first generation of antisense drugs entering clinical trials for the treatment of patients with chronic HCV infection which show acceptable properties for drug development [ 21 ]. (hindawi.com)
Treatment of primary cultures with antisense oligonucleotides for 48 hr before and during TMT treatment significantly protected neurons from the neurotoxic and apoptotic effects of TMT. (aspetjournals.org)
111 In-Labeled antisense, which hybridized with N- myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. (snmjournals.org)
To understand the significance of RA-A47 downregulation in chondrocytes independent from other effects of TNFalpha, we used an antisense oligonucleotide approach and investigated the effect of this treatment on the expression of molecules related to matrix degradation and production of growth factors for chondrocytic, endothelial, and synovial cells. (prohealth.com)
A combination of docetaxel with EGFR AS resulted in increased cytotoxicity compared with treatment with docetaxel plus EGFR sense oligonucleotides or docetaxel alone after 24 h. (aacrjournals.org)
In conclusion, chronic antisense oligonucleotide treatment provides clear and ongoing benefits to paralumbar skeletal muscle, with associated marked reduction in kyphosis. (edu.au)
This trial was focused on understanding whether treatment with a huntingtin lowering drug called an antisense oligonucleotide or ASO is safe. (theresecrutchermarin.com)
Effects of Repeated Complement Activation Associated with Chronic Treatment of Cynomolgus Monkeys with 2'-O-Methoxyethyl Modified Antisense Oligonucleotide. (semanticscholar.org)

However, the antisense constructs were clearly more potent than their mismatch controls and we conclude that some specificity of action is responsible for this effect. (ehu.es)
The clinical use of antisense technology, however, remained limited due to a relative lack of specificity, slow uptake across the cell membrane and rapid intracellular degradation of the oligonucleotide (13) . (onlinejacc.org)
This and the concomitant high nuclease resistance of LNAs results in unprecedented sensitivity and specificity and makes LNA™ oligonucleotides ideal for use in antisense applications. (microsynth.com)

BNA gapmer antisense RNA oligonucleotides offer greater potency and low toxicity than other modified nucleotide. (biosyn.com)
Gapmer antisense chimeras are designed to have both 2'OMe RNA and BNA in the sequence that retain an RNase H activating domain of DNA (or phosphorothioated DNA). (biosyn.com)
As BNA bases confer significant nuclease resistance, we suggest the placement of phosphorothioate modification of only at the DNA gap and leaving the BNA flank as phosphodiester linkages in chimeric BNA Gapmer antisense oligonucleotides. (biosyn.com)

The compositions form stable hybridization complexes with DNA and can be used for any purpose which involves hybridizing an oligonucleotide to a DNA molecule, such as in antisense procedures. (google.com)
A duplex formed by an antisense molecule and its DNA or RNA target is significantly stabilized by free intercalating agents, thereby enhancing the effectiveness of the antisense molecule. (google.com)
Such intercalating agents have been found to stabilize such duplexes even when covalently bound to the antisense molecule. (google.com)

Oligonucleotides are unmodified or chemically modified single-stranded DNA molecules. (aacrjournals.org)

This new generation of modified nucleotide bases can be inserted in a chimeric antisense oligonucleotide that contains a block of BNA nucleobases which increase the target affinity and protect the internal block from nuclease degradation. (biosyn.com)
In addition, the degradation products of phosphodiester oligonucleotides, dNMP 2 mononucleotides, may be cytotoxic and also exert antiproliferative effects ( 7 ). (aacrjournals.org)
Targeted degradation of mRNA in Xenopus oocytes and embryos directed by modified oligonucleotides: studies of An2 and cyclin in embryogenesis. (synbio-tech.com)

Human SK-N-DZ neuroblastoma cells (5 × 10 6 cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111 In-labeled antisense (40 MBq/2 nmol of oligonucleotides/μmol of total phospholipids) that had an average diameter of 250 nm. (snmjournals.org)
Nonradiolabeled antisense, 111 In-labeled sense, or empty cationic REVs were used as controls. (snmjournals.org)

Untreated cells and bcl-xl sense oligonucleotides were controls. (nih.gov)
Application of ion pair chromatography coupled with mass spectrometry to assess antisense oligonucleotides concentrations in living cells. (bioportfolio.com)
Results: Cell viability was most affected with the 15999 antisense oligonucleotides plus IC 50 cisplatin combination (70% of I-45 and 90% of REN cells killed), and apoptosis was markedly increased with this combination by all measures. (aacrjournals.org)
Conclusions: Exposure of human MPM cells to bcl-xl antisense oligonucleotides sensitizes human mesothelioma cells to the conventional chemotherapeutic agent cisplatin. (aacrjournals.org)
FITC-oligonucleotides were taken-up by spleen cells. (egms.de)
We investigated the therapeutic effect of Auger electrons emitted by 111 In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N- myc was overexpressed. (snmjournals.org)
SCCHN cells lines and xenografts were treated with an EGFR AS oligonucleotide targeting region 760-779 of EGFR mRNA (GenBank accession XM_004738 ) alone and in combination with docetaxel. (aacrjournals.org)
This investigation compared antiestrogen-mediated growth arrest with the molecular events after repression of c-Myc expression in MCF-7 breast cancer cells using an antisense oligonucleotide. (garvan.org.au)
Growth was inhibited up to 88% by anti-gastrin oligonucleotides in a dose-related fashion compared to cells treated with diluent or a randomized sequence with the same composition as the anti-gastrin oligonucleotide. (elsevier.com)
Despite several advancements at clinical levels, the delivering of active oligonucleotide to the actual site within target cells is still one of the major challenges hindering the growth of the global antisense oligonucleotides market. (marketresearchreports.biz)
Infusion of an ERβ antisense oligonucleotide into the third ventricle in the vicinity of the AVPV resulted in significantly longer days of successive estrus and a 50% reduction in the number of ERβ-immunoreactive cells in the AVPV. (pnas.org)
They represent the 2 sides to transferring DNA into cells: one is the sense approach (ie, the normal DNA sequence direction), and the other is the antisense approach (ie, the opposite DNA sequence direction). (ahajournals.org)

Anatomy10

Organisms9

Diseases1

Chemicals and Drugs117

Analytical, Diagnostic and Therapeutic Techniques and Equipment44

Phenomena and Processes78

Disciplines and Occupations2

Technology, Industry, Agriculture3

Information Science3

Health Care2

Requirement of a novel gene, Xin, in cardiac morphogenesis. (1/4678)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (2/4678)

The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells. (3/4678)

Upstream region of rat serum albumin gene promoter contributes to promoter activity: presence of functional binding site for hepatocyte nuclear factor-3. (4/4678)

Hyperoxia induces the neuronal differentiated phenotype of PC12 cells via a sustained activity of mitogen-activated protein kinase induced by Bcl-2. (5/4678)

Simultaneous antisense inhibition of two starch-synthase isoforms in potato tubers leads to accumulation of grossly modified amylopectin. (6/4678)

Regulation of cardiac L-type Ca2+ channel by coexpression of G(alpha s) in Xenopus oocytes. (7/4678)

Oligonucleotide-europium complex conjugate designed to cleave the 5' cap structure of the ICAM-1 transcript potentiates antisense activity in cells. (8/4678)

Oligonucleotides, Antisense

Oligonucleotides

RNA, Antisense

DNA, Antisense

Oligodeoxyribonucleotides, Antisense

Antisense Elements (Genetics)

Base Sequence

Oligoribonucleotides, Antisense

Oligodeoxyribonucleotides

Molecular Sequence Data

Oligoribonucleotides

Phosphorothioate Oligonucleotides

Thionucleotides

RNA, Messenger

Nucleic Acid Conformation

DNA

Oligonucleotide Probes

Nucleic Acid Denaturation

Ribonuclease H

RNA

Nucleic Acid Hybridization

Transfection

Transcription, Genetic

Tumor Cells, Cultured

Morpholinos

Peptide Nucleic Acids

Organophosphorus Compounds

Cloning, Molecular

Polymerase Chain Reaction

Amino Acid Sequence

Cell Division

Cell Line

Cells, Cultured

DNA-Binding Proteins

Gene Expression

DNA, Single-Stranded

Nucleic Acids

DNA Primers

Promoter Regions, Genetic

Gene Expression Regulation

Down-Regulation

Base Pairing

Binding Sites

Plasmids

Kinetics

Indicators and Reagents

DNA, Complementary

Zebrafish

Transcription Factors

Guanine

Ribonuclease T1

Reverse Transcriptase Polymerase Chain Reaction

Escherichia coli

Ribonucleases

Apoptosis

RNA, Viral

Blotting, Northern

Psoralens

Gene Targeting

HeLa Cells

Nucleic Acid Heteroduplexes

DNA Probes

Intercalating Agents

Genetic Therapy

Base Composition

Blotting, Western

Fluorescent Dyes

Cell Line, Tumor

Zebrafish Proteins

Mutation

Genes, Synthetic

Genetic Vectors

Exons

Base Pair Mismatch

Molecular Structure

Phosphoric Acids

Gene Silencing

Substrate Specificity

Protein Biosynthesis

Temperature