Antisense oligodeoxynucleotides are typically targeted to bind mRNA sequences, leading to inhibition of gene expression by activation of RNase H to cleave the mRNA, obstruction of translation, alteration of splicing, or other mechanisms. The experimental determination of an effective antisense DNA to inhibit the expression of a particular gene product is expensive and time-consuming, and efforts have long been made to develop a procedure for the rational design of antisense DNA sequences based on properties such as the DNA:RNA hybrid stability, the region of the mRNA being targeted, and the secondary structures of the mRNA and DNA (reviewed by Chan et al. [1]). Programs using in vitro thermodynamic information for intrastrand and interstrand DNA and RNA interactions can be used to help discriminate weak from potent antisense DNA sequences [2, 3]. While extremely important for understanding stabilities of base pairs in vitro, the underlying thermodynamic information in such programs (e.g. the ...
Antisense Nucleotides Antisense nucleotides are strings of RNA or DNA that are complementary to sense strands of nucleotides. They bind to and inactivate these sense strands. They have been used in research, and may become useful for therapy of certain diseases.
Subject population. The investigators will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense.. Treatment plan. EGFR AS will be administered by direct intratumoral injection using direct visualization, endoscopy, or imaging-guidance (ultrasound) as clinically determined (see protocol). Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense (or less if there is no identifiable tumor) starting 2 weeks prior to radiation (study schema in protocol). Patients will receive standard radiation 70 Gy/200 cGy/daily, 5 days/week, with concurrent cetuximab 250 mg/m2, after a loading dose of 400 mg/m2 2 weeks prior to starting radiation.. Statistical Design and Sample Size. The study will be conducted in two-stages. In the first stage, 11 patients with stage IVA-C or recurrent disease will be evaluated for safety. If the regimen is deemed safe, a total of 31 patients with stage III or IVA-B, previously untreated SCCHN will be enrolled ...
HOUSTON, June 28, 2016-- Bio-Path Holdings, Inc.,, a biotechnology company leveraging its proprietary DNAbilize™ liposomal delivery and antisense technology to develop a portfolio of targeted nucleic acid drugs, today announced that it has entered into a sponsored research agreement with Thomas Jefferson University to investigate DNAbilize™ antisense DNA...
C12N15/113-Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing ...
Organs suffer damage when they are removed from a donors body and prepared for transplantation. Temporary loss of blood flow deprives them of oxygen and causes cells to die. Using gene therapy, researchers have found a way to prevent this tissue damage.. Low levels of oxygen increase the activity of the Fas gene, which is known to trigger cell death, or apoptosis. Researchers led by John Fung, of the University of Pittsburgh Medical Center in Pennsylvania, reasoned that blocking the activity of Fas may prevent cell death and help preserve donated organs. Fungs team delivered antisense DNA which specifically blocks the activity of the Fas gene to mice five days before blocking blood flow to the kidney. The flow was blocked for 90 minutes and then allowed to resume. The loss of blood flow to the kidney for periods as short as 30 minutes dramatically increased the activity of the Fas gene. Substantially fewer dead cells were found in the kidneys of mice that had received the anti-Fas DNA. Normal ...
What is the antisense DNA sequence that would be found in the template strand for the information sequence that you submitted as an answer for the previous question? Be sure to note the 5 and 3 ends ...
Histone acetylation is important in regulating DNA accessibility. Multifunctional Sin3 proteins bind histone deacetylases (HDACs) to assemble silencing complexes that selectively target chromatin. We show that, in fission yeast, an essential HDAC, Clr6, exists in two distinct Sin3 core complexes. Complex I contains an essential Sin3 homolog, Pst1, and other factors, and predominantly targets gene promoters. Complex II contains a nonessential Sin3 homolog, Pst2, and several conserved proteins. It preferentially targets transcribed chromosomal regions and centromere cores. Defects in complex II abrogate global protective functions of chromatin, causing increased accessibility of DNA to genotoxic agents and widespread antisense transcripts that are processed by the exosome. Notably, the two Clr6 complexes differentially repress forward and reverse centromeric repeat transcripts, suggesting that these complexes regulate transcription in heterochromatin and euchromatin in similar manners, including
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Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders ...
Pdpk1 - Pdpk1 (untagged ORF) - Rat 3-phosphoinositide dependent protein kinase-1 (Pdpk1), (10 ug) available for purchase from OriGene - Your Gene Company.
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An important new collection of clinical and preclinical reports on genetic therapy, this book describes illustrative examples of diseases in which gene-based interventions are presently plausible, and presents case studies of current research usingMoreAn important new collection of clinical and preclinical reports on genetic therapy, this book describes illustrative examples of diseases in which gene-based interventions are presently plausible, and presents case studies of current research using both synthetic oligonucleotides and biological vectors.Combining the insights of over 50 contributors, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectorsfurnishes a historical overview of genetic therapyhighlights official Food and Drug Administration positions on the preparation of oligonucleotides and vectorsoffers practical models of agent preparation, animal testing, pharmacokinetics, toxicology, and clinical trialsdiscusses both synthetic DNA and biological vector approaches to ...
One major challenge to antisense technology (and RNAi) is the difficulty of getting it into the body. Delivery of the treatment to the brain, for use in diseases like HD, is especially challenging because it must cross the blood-brain barrier. Brain entry is very difficult and cannot be accomplished through a simple injection or pill that contains the antisense oligos. Isis Pharmaceuticals, the leading company in antisense technology, plans to solve this problem by inserting a pump into the chest that can carry the drug to the brain through a catheter, or tube. Another possible solution is to use an inactivated virus to infect cells with the drug.. The second major challenge to antisense technology is its inevitable toxic effects. Although antisense technology is engineered to be very specific, it can still cause unintended damage because it would regulate both the mutant and normal Huntington alleles. The challenge is to determine the right dosage and composition of an antisense molecule to ...
Antonio MANCARELLA (from February 2014). The genome of HIV-1 harbors the three common retroviral genes (gag, pol, and env), in addition to two regulatory genes (tat and rev) and four accessory genes (vif, vpr, vpu, and nef). All of these genes are expressed through a single transcript initiating from the 5 long terminal repeat (LTR), in which the promoter is located. The various viral proteins are synthesized from unspliced, monospliced, or multispliced forms of this major transcript and then assume their functional roles in infected cells.. Recently, several data have suggested that another gene, encoding a product named HIV antisense protein (ASP), may be expressed through an antisense transcript. Antisense transcription encoding proteins involved in the modulation of transactivation potential of multiple cellular transcription activators has been shown in HTLV. Antisense transcription has also been suggested for HIV-1, based on the identification of conserved ORFs in the antisense strand of ...
A targeted approach to treating toxoplasmosis, a parasitic disease, shows early promise in test-tube and animal studies, where it prevented the parasites from making selected proteins. When tested in newly infected mice, ...
siRNA sequence conversion tool. Use this tool to convert DNA target sequence to siRNA sense and antisense sequence or to convert siRNA antisense sequence to DNA sequence ...
Baculovirus IAP (inhibitor-of-apoptosis) genes originated by capture of host genes. Unmodified short antisense DNA oligonucleotides (oligoDNAs) from baculovirus IAP genes can down-regulate specific gene expression profiles in both baculovirus-free and baculovirus-infected insects. In this study, gypsy moth (Lymantria dispar) larvae infected with multiple nucleopolyhedrovirus (LdMNPV), and LdMNPV-free larvae, were treated with oligoDNA antisense to the RING (really interesting new gene) domain of the LdMNPV IAP-3 gene. The results with respect to insect mortality, biomass accumulation, histological studies, RT-PCR, and analysis of DNA apoptotic fragmentation suggest that oligoRING induced increased apoptotic processes in both LdMNPV-free and LdMNPV-infected insect cells, but were more pronounced in the latter. These data open up possibilities for promising new routes of insect pest control using antisense phosphodiester DNA oligonucleotides.
An expression vector containing a cDNA complementary to 1.3 kb of the 5′ coding sequences of the fibronectin gene in the antisense orientation with respect to its promoter was introduced by electroporation into hybrids between melanoma cells and normal fibroblasts in which malignancy was suppressed. Immunofluorescence analysis of clones transfected with the antisense cDNA showed a dramatic decrease in the amount of fibronectin on the cell surface compared to that seen on the surface of the untransfected hybrid cells or of cells transfected with fibronectin cDNA in the sense orientation or with the expression vector alone. Four out of five clones transfected with the antisense cDNA were highly tumorigenic, whereas transfectants containing either the sense fibronectin construct or the expression vector alone remained non-tumorigenic. These results suggest that antisense RNA to fibronectin may be able to abrogate the suppression of malignancy imposed on the hybrid cells by the fibroblast parent. ...
Recent studies had found thousands of natural antisense transcripts originating from the same genomic loci of protein coding genes but from the opposite strand. It is unclear whether the majority of antisense transcripts are functional or merely transcriptional noise. Using the Affymetrix Exon array with a modified cDNA synthesis protocol that enables genome-wide detection of antisense transcription, we conducted large-scale expression analysis of antisense transcripts in nine corresponding tissues from human, mouse and rat. We detected thousands of antisense transcripts, some of which show tissue-specific expression that could be subjected to further study for their potential function in the corresponding tissues/organs. The expression patterns of many antisense transcripts are conserved across species, suggesting selective pressure on these transcripts. When compared to protein-coding genes, antisense transcripts show a lesser degree of expression conservation. We also found a positive correlation
The Arabidopsis genome contains a large number of gene pairs that encode sense and antisense transcripts with overlapping 3′ regions, indicative for a potential role of natural antisense transcription in regulating sense gene expression or transcript processing. When we mapped poly(A) transcripts of three plant gene pairs with long overlapping antisense transcripts, we identified an unusual transcript composition for two of the three gene pairs. Both genes pairs encoded a class of long sense transcripts and a class of short sense transcripts that terminate within the same polyadenylation region as the antisense transcripts encoded by the opposite strand. We find that the presence of the short sense transcript was not dependent on the expression of an antisense transcript. This argues against the assumption that the common termination region for sense and antisense poly(A) transcripts is the result of antisense-specific regulation. We speculate that for some genes evolution may have especially ...
In article ,57e912$jfb at kadri.ut.ee,, mspeek at tamm.eenet.ee says... , ,Elizabeth Rosenberg (erosenbe at gpu2.srv.ualberta.ca) wrote: ,: Hi! , ,: Our group is about to embark on the glorious journey of downregulation of ,: a gene by use of antisense constructs. We are very new to this, and would ,: appreciate any and all feedback anyone might have. ,: Now we would like to insert an antisense fragment of the same gene into ,: the pREP10 vector and tranfect this construct into normal CHO cells that ,: are the parent of our mutant strain. ,I would not recommend antisense experiments such as yours. This is because ,it is remarkably inefficient (for review see NAR 21:4383-91 (1993)) ,I spent 1.5 yrs to study RNA-RNA hybridization/annealing between ,a pair of naturally occurring sense-antisense mRNAs, but found ,very little of them in duplex (Mol. Endo.9:1655-65 (1995)) ,Mart (mspeek at ebc.ee in Estonia) I would also think that you may need several, if not many very good controls. I have seen ...
Hoxa 11 is a murine Abdominal-B-type homeobox gene. The structure of this gene is presented, including genomic and cDNA sequence. The cDNA includes the complete open reading frame and based on primer extension results is near full length. Surprisingly, the antisense strand of Hoxa 11 was found to be transcribed. Moreover, these antisense transcripts were processed and polyadenylated. The developmental expression patterns for both sense and antisense transcripts were examined using serial section and whole-mount in situ hybridizations. Hoxa 11 transcription patterns were defined in the limbs, kidney and stromal cells surrounding the Mullerian and Wolffian ducts. Of particular interest, in the developing limbs, the sense and antisense transcripts showed complementary expression patterns, with antisense RNAs increasing in abundance in regions where sense RNAs were diminishing in abundance. Furthermore, targeted mutation of Hoxa 11 is shown to result in both male and female sterility. The female ...
As a leader in the field, the directors believe that Ionis is the ideal technology partner for Antisense Therapeutics. Ionis is a leading drug discovery and development company, focused exclusively on the therapeutic target, RNA. Founded in 1989, Ionis mission is to develop products from its RNA-based technology antisense.. California-based Ionis is the leader in all aspects of antisense technology advancement, including mechanism research, the development of new chemistries, novel formulations and innovative drugs. The company currently has over 30 drugs in development to treat a wide variety of diseases with an emphasis on neurological, cardiometabolic, severe and rare diseases and cancer.. ...
Today, Insights is synonymous with UPSC civil services exam preparation. Insights has redefined the way preparation is done in UPSC civil service exam. ...
Synonyms for antisense in Free Thesaurus. Antonyms for antisense. 25 synonyms for strand: filament, fibre, thread, length, lock, string, twist, rope, wisp, tress, component, part, element, ingredient, constituent, feature.... What are synonyms for antisense?
Antisense oligos containing phosphorothioate bonds can be used in medium containing serum. However, it is recommended that you inactivate the exonucleases in the serum to decrease the chances of degredation even when protecting modifications (such as phosphorothioate bonds) are present. Exonuclease inactivation can be accomplished by heat inactivatation at 65°C (instead of 56°C) for 30 minutes. The half life of such an antisense oligo will be dependent on the target transcript, the cell type, and the antisense construct, resulting in no set average for this number. There are reports of antisense oligos lasting 24 hours in vivo (mice ...
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Transcript detection by RISH using antisense and sense probes.(A and B) AT5G05160/RUL1, (C and D) PXY, (E and F) ATHB8, (G and H) AT5G51350/MOL1, (I and J) AGO4
I would like to transcribe both the sense and antisense strands of a clone in some type of high-copy number plasmid. Basically, I need a plasmid that has two identical (and ideally inducible) promoters just upstream of the MCS on each strand. It should look something like this ...
Antisense refers to segments of synthesized genetic material which can prevent or combat diseases. This word has come into common biomedical...
Author: Stitt, M. et al.; Genre: Journal Article; Published in Print: 1991; Keywords: flux control (photosynthesis)|br/|nicotiana (transformed with antisense DNA)|br/|ribulose-1,5-bisphosphate carboxylase-oxygenase (control of photosynthesis)|br/|transgenic plant (antisense)|br/|c-3 plants|br/|leaves|br/|limitations|br/|metabolism|br/|phosphate|br/|nitrogen|br/|fixation; Title: Decreased Ribulose-1,5-Bisphosphate Carboxylase-Oxygenase in Transgenic Tobacco Transformed with Antisense Rbcs. 2. Flux-Control Coefficients for Photosynthesis in Varying Light, Co2, and Air Humidity
TY - JOUR. T1 - PPARγ ligands attenuate mesangial contractile dysfunction in high glucose. AU - Ueta, Maki. AU - Wakisaka, Masanori. AU - Ago, Tetsuro. AU - Kitazono, Takanari. AU - Nakamura, Udai. AU - Yoshinari, Mototaka. AU - Iwase, Masanori. AU - Iida, Mitsuo. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2004/3. Y1 - 2004/3. N2 - Background. To elucidate the regulation of peroxisome proliferator- activated receptor γ (PPARγ) and its roles in mesangial cells, we examined the expression of PPARγ1 and effects of its ligands on cell phenotypes and angiotensin II-induced contractile response in cultured rat mesangial cells under a high (20 mmol/L) glucose condition. Methods. The effects of tumor necrosis factor α (TNFα), protein kinase C (PKC) activation, antisense DNA for PPARγ1, PPARγ ligands and PD98059 were examined in mesangial cells cultured in either 5 mmol/L or 20 mmol/L glucose. The expressions of PPARγ1 protein and α-smooth muscle actin (αSMA) as a ...
Antisense transcription is widespread in genomes. Despite large differences in gene size and architecture, we find that yeast and human genes share a unique, antisense transcription-associated chromatin signature. We asked whether this signature is related to a biological function for antisense transcription. Using quantitative RNA-FISH, we observed changes in sense transcript distributions in nuclei and cytoplasm as antisense transcript levels were altered. To determine the mechanistic differences underlying these distributions, we developed a mathematical framework describing transcription from initiation to transcript degradation. At GAL1, high levels of antisense transcription alter sense transcription dynamics, reducing rates of transcript production and processing, while increasing transcript stability. This relationship with transcript stability is also observed as a genome-wide association. Establishing the antisense transcription-associated chromatin signature through disruption of the Set3C
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The Finkel-Biskis-Reilly murine sarcoma virus (FBR-MuSV) is capable of inducing osteosarcomas in susceptible mice. This retrovirus transduced sequences derived from the transcription factor c-fos and from an unrelated mouse sequence called fox. Here, we describe the cloning and sequence analysis of human and mouse cellular cDNAs hybridizing to the fox sequence. The cloned cDNAs encode for a single ubiquitin-like (Fubi) protein fused in frame to S30, a protein of the small ribosomal subunit. Fubi conserved amino acid residues known to be involved in the ATP-dependent proteolytic activity of ubiquitin. Moreover, the fau gene is conserved in several species, while its mRNA is ubiquitously expressed in different mouse tissues. Surprisingly, FBR-MuSV transduced the complete but mutated open reading frame (ORF) in its reversed transcriptional orientation. This is the first report about a retrovirus in which an antisense sequence to a cellular gene, which we called fau (FBR-MuSV-associated ubiquitously ...
TY - JOUR. T1 - Potent and nontoxic antisense oligonudeotides containing locked nucleic acids. AU - Wahlestedt, Claes. AU - Salmi, Peter. AU - Good, Liam. AU - Kela, Johanna. AU - Johnsson, Thomas. AU - Hökfelt, Tomas. AU - Broberger, Christian. AU - Porreca, Frank. AU - Lai, Josephine. AU - Ren, Kunkun. AU - Ossipov, Michael. AU - Koshkin, Alexei. AU - Jakobsen, Nana. AU - Skouv, Jan. AU - Oerum, Henrik. AU - Jacobsen, Mogens Havsteen. AU - Wengel, Jesper. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 2000/5/9. Y1 - 2000/5/9. N2 - Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of ...
HIV-based antisense vectors may provide several important advantages over current HIV combination therapies. VIRxSYS Corporation (VIRxSYS) is developing the candidate clinical vector VRX496. VRX496 is an HIV-based lentiviral vector containing an anti-HIV antisense sequence targeted to the HIV envelope (env) coding sequence. First, HIV-1 vectors are likely to be less toxic than current combination drug therapies because the genetic antisense antiviral is expressed only in cells that become infected with wt-HIV. The payload is located upstream of a major splice acceptor site and is thus dependent on the expression of Tat and Rev proteins that are provided by wt-HIV. Second, the length of the antisense region is over 900 nucleotides long, making it difficult for wt-HIV to create resistant strains that are sufficiently fit to cause disease. Third, HIV vectors are predicted to be safe because no novel genetic sequences are introduced into the patient (i.e., no novel functional genes are contained in ...
One difference between metabolism in cancer and normal cells is the switch in cancer to the production of a different version, or isoform, of a protein produced from the pyruvate kinase-M (PK-M) gene. The protein version produced in normal cells is known as PK-M1, while the one produced by cancer cells is known as PK-M2.. PK-M2 is highly expressed in a broad range of cancer cells. It enables the cancer cell to consume far more glucose than normal, while using little of it for energy. Instead, the rest is used to make more material with which to build more cancer cells.. PK-M1 and PK-M2 are produced in a mutually exclusive manner - one-at-a-time, from the same gene, by a mechanism known as alternative splicing. When a genes DNA is being copied into the messenger molecule known as mRNA, the intermediate template for making proteins, a cellular machine called the spliceosome cuts and pastes different pieces out of and into that mRNA molecule.. The non-essential parts that are edited out are known ...
Title: DNA Drug Design for Cancer Therapy. VOLUME: 11 ISSUE: 22. Author(s):Y. S. Cho-Chung. Affiliation:Cellular Biochemistry Section, BRL, CCR, National Cancer Institute, Bldg. 10, Rm. 5B05, 9000Rockville Pike, Bethesda, MD 20892-1750, USA.. Keywords:antisense, oligonucleotides, dna drugs, gene expression, cancer, growth inhibition, transcription factor decoy. Abstract: DNA (antisense and other oligonucleotides) drug design represents a direct genetic approach for cancer treatment. Such an approach takes advantage of mechanisms that activate genes known to confer a growth advantage to neoplastic cells. The ability to block the expression of these genes allows exploration of normal growth regulation. Progress in DNA drug technology has been rapid, and the traditional antisense inhibition of gene expression is now viewed on a genomic scale. This global view has led to a new vision in antisense technology, the elimination of nonspecific and undesirable side effects, and ultimately the generation ...
Less than a year ago, Eli Lilly and Co. and Isis Pharmaceuticals Inc. signed a deal for Isis antisense technology worth as much as $400 million. On Tuesday the companies expanded that deal, opening it up to include specific gene targets for cancer and adding to its total value. (BioWorld Today)
Antisense compounds, compositions and methods are provided for modulating the expression of C-reactive protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C-reactive protein. Methods of using these compounds for modulation of C-reactive protein expression and for treatment of diseases associated with expression of C-reactive protein are provided.
Perform reliable qPCR with Bio-Rads pre-validated POLDIP3 primer pair, for the Zebrafish genome. Designed for SYBR Green-based detection.
Inhibition of translation initiation by antisense oligonucleotides via an RNase-H independent mechanism.: We have used alpha-oligomers as antisense oligonucleot
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Gymnosis combines specifically modified antisense oligos with a cells normal growth properties to achieve sequence-specific target knockdown without the need for transfection reagents or serum additives, according to its developers.
We have shown that in human cells, an antiserum generated against a recombinant UBPY fragment recognizes a protein doublet of Mr 130 000, in good agreement with the predicted UBPY mol. wt of 127 500 Da. The UBPY bands were enhanced upon transfection of a sense UBPY cDNA and, most importantly, were lowered in abundance upon transfection of an antisense cDNA construct. UBPY was able to remove ubiquitin from ubiquitin adducts. Its expression was undetectable upon serum starvation of normal human fibroblasts, and the protein reappeared upon re‐stimulation, in mid G1 coincident with the accumulation of cyclin D1. UBPY levels were reduced in non‐immortalized cells as they reached confluence and arrested in G0, while they remained high and even increased in transformed cells.. To date, no other studies have demonstrated the effects of down‐regulating a UBP in mammalian cells. We have been able to inhibit UBPY accumulation using an antisense cDNA vector and could demonstrate that G0‐arrested ...
The IAP survivin deserves attention as a target for cancer therapy due to its differential expression in tumors versus normal tissues. It is expressed during embryonal development, lacks expression in terminally differentiated adult tissues, and becomes reexpressed in transformed cell lines and a variety of human tumors, with highest levels being found in breast and lung cancer (1) . The expression of survivin in tumors is correlated with drug resistance and/or shorter survival of patients with non-small cell lung cancer (5) , colorectal cancer (7) , and neuroblastoma (9) . Despite recognition that survivin represents an attractive target for cancer therapy (2, 3, 4, 5, 6, 7, 8, 9, 10) , mainly survivin antisense cDNA fragments (11 , 12) and very recently also antisense oligonucleotides (13) have been used to elucidate the role of survivin during cell division and apoptosis. In the present study, we describe an antisense oligonucleotide approach to down-regulate survivin expression in the lung ...
Eukaryotic cells express a complex layer of noncoding RNAs. An intriguing family of regulatory RNAs includes transcripts from the opposite strand of protein coding genes, so called natural antisense transcripts (NATs). Here, we test the hypothesis that antisense transcription triggers RNA interference and gives rise to endogenous short RNAs (endo-siRNAs). We used cloned human embryonic kidney cells (HEK293) followed by short RNAseq to investigate the small genic RNA transcriptome. 378 genes gave rise to short RNA reads that mapped to exons of RefSeq genes. The length profile of short RNAs showed a broad peak of 20-24 nucleotides, indicative of endo-siRNAs. Collapsed reads mapped predominantly to the first and the last exon of genes (74%). RNAs reads were intersected with sequences occupied by RNAPII or bound to Argonaute (AGO1 by crosslinking, ligation, and sequencing of hybrids, CLASH). In the first exon, 94% of the reads correlated with RNAPII occupancy with an average density of 130 (relative units);
The stacked soybean line MON-877Ø5-6 x MON-877Ø8-9 x MON-89788-1 was obtained through the traditional cross breading of each of the parental organisms to produce an organism that expresses each of Dicamba monooxygenase, EPSPS and results in the antisense suppression of the FATB and FAD2 genes. This results in dicamba and glyphosate herbicide tolerance and a modified fatty acid profile ...
Antisense oligonucleotide is a new approach to treat several neurodegenerative disorders to prevent disease onset or stop disease development.
Basic Research: Scientists from every sector of research (government, academia, non-profit and industry) contribute to understanding the disease process, leading researchers to identify potential disease pathways as drug targets. This step is completed using a variety of experimental tools including biochemical analysis of proteins involved in the disease and model development using cell and animal models in the laboratory.. Drug Discovery: A variety of treatment approaches are in development for ALS including small molecule approaches, gene therapy approaches and antisense technologies. Researchers in industry and academia identify appropriate chemical entities based on pathways believed to be relevant to the disease. These chemical entities are selected from large screens of thousands of molecules. Those that appear to interact with the target of interest and can be identified by an appropriate read out are selected and further optimized. There are a variety of chemical properties that are ...
Pairs of RNA molecules transcribed from partially or entirely complementary loci are called cis-natural antisense transcripts (cis-NATs), and they play key roles in the regulation of gene expression in many organisms. A promising experimental tool for profiling sense and antisense transcription is strand-specific RNA sequencing (ssRNA-seq). To identify cis-NATs using ssRNA-seq, we developed a new computational method based on model comparison that incorporates the inherent variable efficiency of generating perfectly strand-specific libraries. Applying the method to new ssRNA-seq data from whole root and cell-type specific Arabidopsis libraries confirmed most of the known cis-NAT pairs and identified hundreds of additional cis-NAT pairs.. ...
Antisense oligonucleotides (ASOs) are short, synthetic 15-25 nt oligonucleotides that localize to the nucleus used to inhibit gene expression.
COMPREHENSIVE LONG-TERM PLATFORM AGREEMENT FOR THE DEVELOPMENT OF NOVEL ANTISENSE OLIGONUCLEOTIDE THERAPEUTICS ACROSS A BROAD RANGE OF TARGETS AND INDICATIONS
Alan D. B. Malcolm; Uses of antisense nucleic acids - an introduction. Biochem Soc Trans 1 November 1992; 20 (4): 745-746. doi: https://doi.org/10.1042/bst0200745. Download citation file:. ...
From BioPortfolio: SummaryAntisense Therapeutics Ltd Antisense Therapeutics is clinical staged biopharmaceutical company which focuses on the discovery, development and commercial...
This article describes the advancement of SAGE, to include LongSage, RL-Sage and Super-SAGE techniques that have greater capabilities.
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Vico Therapeutics has raised $31 million (€27 million) in a Series A financing round, which the company will use to further advance its Antisense OligoNucleotides lead platform.
What? Can antisense possibly be hot again? Many people wondered if the decades-old RNA-targeting approach to drug development was even still alive. But