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  • genome
  • Technological advances have revolutionized the genome-scale profiling of DNA copy number and sequence, DNA and chromatin modification, and gene expression and have substantially enhanced our understanding of the molecular changes that underlie many cancers. (cancer.gov)
  • In contrast, when genes are knocked out, they are completely erased from the organism's genome and, thus, have no expression. (wikipedia.org)
  • The enzyme uses the viral RNA genome as a template for the synthesis of a complementary DNA copy. (wikipedia.org)
  • Integrase processes the LTR before inserting the viral genome into the host DNA. (wikipedia.org)
  • This construct was designed to express three therapeutic RNAs, one of which was a shRNA, thereby combating HIV replication in three different ways: shRNA, that silences the tat and rev genes of the HIV genome CCR5 ribozyme, inhibiting viral cell entry TAR decoy RNA, inhibiting initiation of viral transcription. (wikipedia.org)
  • To the extent it is useful to craft a distinction between these related concepts, RNA silencing may be thought of as referring to the broader scheme of small RNA related controls involved in gene expression and the protection of the genome against mobile repetitive DNA sequences, retroelements, and transposons to the extent that these can induce mutations. (wikipedia.org)
  • By delivering the Cas9 nuclease complexed with a synthetic guide RNA (gRNA) into a cell, the cell's genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added. (wikipedia.org)
  • Subsequent analysis has shown that the transformation was brought about by inserting ~4.5 kilobases from the left arm of the viral genome, which became incorporated into human chromosome 19. (wikipedia.org)
  • molecules
  • These molecules can be composed of single-stranded DNA or RNA and are generally 13-25 nucleotides long. (wikipedia.org)
  • Ribozymes are catalytic RNA molecules used to inhibit gene expression. (wikipedia.org)
  • These molecules work by cleaving mRNA molecules, essentially silencing the genes that produced them. (wikipedia.org)
  • Sidney Altman and Thomas Cech first discovered catalytic RNA molecules, RNase P and group II intron ribozymes, in 1989 and won the Nobel Prize for their discovery. (wikipedia.org)
  • These catalytic RNA molecules bind to a specific site and attack the neighboring phosphate in the RNA backbone with their 2' oxygen, which acts as a nucleophile, resulting in the formation of cleaved products with a 2'3'-cyclic phosphate and a 5' hydroxyl terminal end. (wikipedia.org)
  • this is what enables the molecules to form the RNA-Induced Silencing Complex (RISC). (wikipedia.org)
  • The closely related technique of quantitative PCR permits the quantitative measurement of DNA or RNA molecules and is used to estimate the densities of the reference pathogens in food, water and environmental samples. (wikipedia.org)
  • Gel electrophoresis is used routinely in microbiology to separate DNA, RNA, or protein molecules using an electric field by virtue of their size, shape or electric charge. (wikipedia.org)
  • Southern blotting, northern blotting, western blotting and Eastern blotting are molecular techniques for detecting the presence of microbial DNA sequences (Southern), RNA sequences (northern), protein molecules (western) or protein modifications (Eastern). (wikipedia.org)
  • RNAs are the direct products of genes, and these small RNAs can bind to other specific messenger RNA (mRNA) molecules and either increase or decrease their activity, for example by preventing an mRNA from being translated into a protein. (wikipedia.org)
  • Following export from the nucleus by exportin-5, pre-mir-155 molecules are cleaved near the terminal loop by Dicer resulting in RNA duplexes of ~22nucleotides. (wikipedia.org)
  • Once miR-155-5p/-3p is assembled into the RISC, these molecules subsequently recognize their target messenger RNA (mRNA) by base pairing interactions between nucleotides 2 and 8 of miR-155-5p/-3p (the seed region) and complementary nucleotides predominantly in the 3'-untranslated region (3'-UTR) of mRNAs (see Figure 4 and 5 below). (wikipedia.org)
  • Once released, type I interferons will activate molecules which prevent the virus from producing and replicating its RNA and DNA. (wikipedia.org)
  • protein
  • However, little is known about how tumor cells co-opt cellular processes to express, from rearranged DNA, an in-frame fusion transcript encoding a chimeric functional protein and so we are using functional genetic approaches to identify genes required for the expression or activity of fusion oncoproteins. (cancer.gov)
  • In this study, we designed TaqMan probes and PCR primers based on the yrfH gene encoding a heat shock protein for the iiPCR detection of Salmonella in chicken meat samples. (jove.com)
  • At high titers, not only the shTH vectors but also the scrambled and green fluorescence protein (GFP)-only controls caused cell death. (epfl.ch)
  • By enforced HBx gene expression in cultured HepG2 cells, we determined the effect of HBx on CYP2E1 mRNA and protein expression. (jove.com)
  • Gp41 transmembrane envelope protein TM, also encoded by the viral gene env. (wikipedia.org)
  • P24 capsid protein CA, encoded by the viral gene gag. (wikipedia.org)
  • Following Dicer cleavage, an Argonaute (Ago) protein binds to the short RNA duplexes, forming the core of a multi-subunit complex called the RNA-induced silencing complex (RISC). (wikipedia.org)
  • Another cellular enzyme, RNAse L-also induced by interferon action-destroys RNA within the cells to further reduce protein synthesis of both viral and host genes. (wikipedia.org)
  • In February 2010 researchers reported success in reducing HIV viral load using patient T-cells which had been harvested, modified with an RNA antisense strand to the HIV viral envelope protein, and re-infused into the patient during a planned lapse in retroviral drug therapy. (wikipedia.org)
  • Typically, these experiments involve transfecting in a gene (or combination of genes) of interest, and then analyzing the expressed protein. (wikipedia.org)
  • vivo
  • Development of an safe and efficient in vivo gene delivery method is indispensable for molecular biology research and the progress in the following gene therapy. (frontiersin.org)
  • This method, involving intravenous injection (i.v.) of massive DNA in a short duration, gives a transient but high in vivo gene expression especially in the liver of small animals. (frontiersin.org)
  • The most popular method is plasmid DNA (pDNA)-based gene delivery methods, due to its advantage in safety and versatility in vivo . (frontiersin.org)
  • In vivo delivery of ddRNAi constructs has been demonstrated using a range of vectors and reagents with different routes of administration (ROA). (wikipedia.org)
  • For example, in a Phase I clinical trial at the City of Hope National Medical Center, California, US, four HIV-positive patients with non-Hodgkin's lymphoma were successfully treated with autologous hematopoietic progenitor cells pre-transduced ex vivo with ddRNAi constructs using lentiviral vectors. (wikipedia.org)
  • Exogenous molecular control in vivo of miR-155 expression may inhibit malignant growth, viral infections, and enhance the progression of cardiovascular diseases. (wikipedia.org)
  • Because many variations of DNA and RNA are unstable in in vivo conditions, carriers, such as nanoparticles, are necessary to protect from degeneration by nucleases. (wikipedia.org)
  • replication
  • Furthermore, nucleoside analogs, such as 3TC- lamivudine, impede viral replication but do not directly promote its eradication. (natap.org)
  • The antiviral effect is sequence-specific and does not depend on active viral replication. (natap.org)
  • Although HCV RNA replication has been observed in human non-hepatic and murine cell lines, the efficiency was very low and required long-term selection procedures using HCV replicon constructs expressing dominant antibiotic-selectable markers 1-5 . (jove.com)
  • In both cases, completion of the viral replication cycle is only possible in the heterokaryons. (jove.com)
  • To assess the influence of dominant restrictions on the complete viral life cycle including cell entry, RNA translation, replication and virus assembly, we took advantage of a human liver cell line (Huh-7 Lunet N cells 9 ) which lacks endogenous expression of CD81, an essential entry factor of HCV. (jove.com)
  • Interferons are named for their ability to "interfere" with viral replication by protecting cells from virus infections. (wikipedia.org)
  • Dicer
  • Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. (wikipedia.org)
  • Dicer was given its name in 2001 by Emily Bernstein, a graduate student in Greg Hannon's lab at Cold Spring Harbor Laboratory, who sought to discover the enzyme responsible for generating small RNA fragments from double-stranded RNA. (wikipedia.org)
  • Subsequent experiments testing RNase III family enzymes abilities to create RNA fragments narrowed the search to Drosophila CG4792, now named Dicer. (wikipedia.org)
  • nucleotides in length
  • RNA silencing pathways are associated with the regulatory activity of small non-coding RNAs (approximately 20-30 nucleotides in length) that function as factors involved in inactivating homologous sequences, promoting endonuclease activity, translational arrest, and/or chromatic or DNA modification. (wikipedia.org)
  • polymerase
  • Typical transcription cassettes use an RNA polymerase III promoter (e.g. (wikipedia.org)
  • Reverse transcriptase is the virally encoded RNA-dependent DNA polymerase. (wikipedia.org)
  • The MIR155HG is transcribed by RNA polymerase II and the resulting ~1,500 nucleotide RNA is capped and polyadenylated. (wikipedia.org)
  • A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction, in order to compare the effect of valaciclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. (wikipedia.org)
  • viruses
  • In contrast, other gene delivery methods that do not involve viruses are being extensively studied for use of clinical application. (frontiersin.org)
  • Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. (fitness-vip.com)
  • Some viruses are used as vectors for gene therapy. (wikipedia.org)
  • RNA interference has an important role in defending cells against parasitic nucleotide sequences - viruses and transposons. (wikipedia.org)
  • dUTPase DU encoded by the pro gene (part of pol gene in some viruses), the role of which is still unknown. (wikipedia.org)
  • It focuses on the following aspects of viruses: their structure, classification and evolution, their ways to infect and exploit host cells for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. (wikipedia.org)
  • Three hypotheses regarding their origin exist: Viruses arose from non-living matter, separately from yet in parallel to cells, perhaps in the form of self-replicating RNA ribozymes similar to viroids. (wikipedia.org)
  • The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of viral evolution. (wikipedia.org)
  • In the context in which the phenomenon was first studied, small RNA was found to play an important role in defending plants against viruses. (wikipedia.org)
  • In evolution, viruses are an important means of horizontal gene transfer, which increases genetic diversity. (wikipedia.org)
  • Some viruses including those that cause AIDS and viral hepatitis evade these immune responses and result in chronic infections. (wikipedia.org)
  • Viruses offer an efficient means of delivering genes into cells, which they evolved to do, and are thus of great use as experimental tools. (wikipedia.org)
  • This danger can be avoided by the use of viruses which lack key genes, and which are thus unable to replicate after entering a cell. (wikipedia.org)
  • nucleic
  • Expression of type I and III IFNs can be induced in virtually all cell types upon recognition of viral components, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL-12, and its expression is restricted to immune cells such as T cells and NK cells. (wikipedia.org)
  • inhibit
  • In this study, we tested a hypothesis that HBx may inhibit CYP2E1 gene expression via hepatocyte nuclear factor 4? (jove.com)
  • polyethylene-glycol
  • Provided that cell fusion was initiated by treatment with polyethylene-glycol (PEG), the culture released infectious viral particles which infected naïve cells in a receptor-dependent fashion. (jove.com)
  • endogenous
  • Earlier studies in petunias demonstrated a phenomenon (termed co-suppression) where over-expression of a homologous transgene resulted in silencing of both the transgene and the endogenous gene. (sigmaaldrich.com)
  • Proof-of-concept has been demonstrated across a range of disease models, including viral diseases such as HIV, hepatitis B or hepatitis C, or diseases associated with altered expression of endogenous genes such as drug-resistant lung cancer, neuropathic pain, advanced cancer and retinitis pigmentosa. (wikipedia.org)
  • organisms
  • Bioinformatics studies on the genomes of multiple organisms suggest this length maximizes target-gene specificity and minimizes non-specific effects. (wikipedia.org)
  • In general, RNA interference is an essential part of normal processes within organisms such as humans, and it is an area being researched as a diagnostic and therapeutic tool for cancer targets. (wikipedia.org)
  • These disease-bearing organisms are known as vectors. (wikipedia.org)
  • These sequences play a key role in a bacterial defense system, and form the basis of a technology known as CRISPR/Cas9 that effectively and specifically changes genes within organisms. (wikipedia.org)
  • The process of selective breeding, in which organisms with desired traits (and thus with the desired genes) are used to breed the next generation and organisms lacking the trait are not bred, is a precursor to the modern concept of genetic modification. (wikipedia.org)
  • Various advancements in genetics allowed humans to directly alter the DNA and therefore genes of organisms. (wikipedia.org)
  • catalytic
  • Several years ago, when the discovery of catalytic RNA was recognized in a public manner,many people asked if new ?elds of therapy would soon be available. (ebooks.com)
  • mechanism
  • The antisense oligonucleotides can affect gene expression in two ways: by using an RNase H-dependent mechanism or by using a steric blocking mechanism. (wikipedia.org)
  • The majority of antisense drugs function through the RNase H-dependent mechanism, in which RNase H hydrolyzes the RNA strand of the DNA/RNA heteroduplex. (wikipedia.org)
  • This mechanism has great potential as a novel therapeutic to silence disease-causing genes. (wikipedia.org)
  • Thus, a novel mechanism for regulation of gene expression, the epigenetic silencing of genes by miRNAs, was discovered. (wikipedia.org)
  • cells
  • Dr. Caplen applies the perturbations induced by RNA- or DNA-based technologies to interrogate specific aspects of the genetic, transcriptional, and cell-signaling alterations observed in cancer cells. (cancer.gov)
  • The diversity of RNA and the varied role of it inside cells and in therapy should be a tremendous challenge for young molecular biologists. (ebooks.com)
  • Viral vectors are frequently used because of their intrinsic ability to enter the cells and promote the expression of the gene of interest. (redorbit.com)
  • Moreover, K-ras gene mutation enhances motility of lung adenocarcinoma cells via Akt activation (18), and radioresistance of K-ras-mutated human tumor is mediated through the epidermal growth factor receptor-dependent PI3K-Akt pathway (19). (redorbit.com)
  • RNAa was demonstrated in human cells using synthetic dsRNAs, termed "small activating RNAs" (saRNAs). (wikipedia.org)
  • Virus vectors have been developed that mediate stable genetic modification of treated cells by chromosomal integration of the transferred vector genomes. (wikipedia.org)
  • Gammaretroviral and lentiviral vectors, for example, can be utilized in clinical gene therapy aimed at the long-term correction of genetic defects, e.g., in stem and progenitor cells. (wikipedia.org)
  • Lentiviruses can integrate a significant amount of viral RNA into the DNA of the host cell and can efficiently infect nondividing cells, so they are one of the most efficient methods of gene delivery. (wikipedia.org)
  • Zinc finger nucleases have also been used in a mouse model of haemophilia and a clinical trial found CD4+ human T-cells with the CCR5 gene disrupted by zinc finger nucleases to be safe as a potential treatment for HIV/AIDS. (wikipedia.org)
  • The term virion (plural virions), which dates from 1959, is also used to refer to a single, stable infective viral particle that is released from the cell and is fully capable of infecting other cells of the same type. (wikipedia.org)
  • In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. (wikipedia.org)
  • They also limit viral spread by increasing p53 activity, which kills virus-infected cells by promoting apoptosis. (wikipedia.org)
  • Other methods exploit natural forms of gene transfer, such as the ability of Agrobacterium to transfer genetic material to plants, or the ability of lentiviruses to transfer genes to animal cells. (wikipedia.org)
  • toxicity
  • Our previous study has proven that the poly(ester amine) carrier is less than 150 nm and offers effective delivery potential due to a biodegradable complex formation with genes with little toxicity and enhanced gene transfer efficiency (10). (redorbit.com)
  • enzyme
  • Adenovirus-mediated delivery into myocytes of muscle glycogen phosphorylase, the enzyme deficient in patients with glycogen-storage disease type V. Biochem J 304, 1009-1014. (fitness-vip.com)
  • transgene
  • 2009). Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. (fitness-vip.com)
  • Efficacy of gene therapy for a prototypical lysosomal storage disease (GSD-II) is critically dependent on vector dose, transgene promoter, and the tissues targeted for vector transduction. (fitness-vip.com)
  • Genomic Imprinting Paramutation Transposon silencing (or Histone Modifications) Transgene silencing Position effect RNA-directed DNA methylation RNA interference RNA silencing Nonsense mediated decay Transvection Meiotic silencing of unpaired DNA Antisense oligonucleotides were discovered in 1978 by Paul Zamecnik and Mary Stephenson. (wikipedia.org)
  • pathways
  • The technology of RNA interference emerged in its earliest form following a 1998 study in Caenorhabditis elegans 1 and has since rapidly evolved to its current form as a revolutionary tool for studying gene function, biological pathways, and the physiology of disease. (sigmaaldrich.com)
  • RNA silencing describes several mechanistically related pathways which are involved in controlling and regulating gene expression. (wikipedia.org)
  • It has also been observed that the major RNA silencing pathways currently identified have mechanisms of action which may involve both post-transcriptional gene silencing (PTGS) as well as chromatin-dependent gene silencing (CDGS) pathways. (wikipedia.org)
  • The molecular mechanisms for RNA silencing were initially studied in plants but have since broadened to cover a variety of subjects, from fungi to mammals, providing strong evidence that these pathways are highly conserved. (wikipedia.org)
  • silence
  • In particular, methods used to silence genes are being increasingly used to produce therapeutics to combat cancer and diseases, such as infectious diseases and neurodegenerative disorders. (wikipedia.org)
  • In addition, attempts are being made to use ribozymes to produce gene silencing therapeutics, which would silence genes that are responsible for causing diseases. (wikipedia.org)
  • sequences
  • A range of diverse functions have been proposed for a growing number of characterized small RNA sequences-e.g., regulation of developmental, neuronal cell fate, cell death, proliferation, fat storage, haematopoietic cell fate, insulin secretion. (wikipedia.org)
  • MiRNAs can interact with targets that have similar sequences, which inhibits translation of different genes. (wikipedia.org)
  • Small clusters of cas (CRISPR-associated system) genes are located next to CRISPR sequences. (wikipedia.org)
  • small
  • Other classes of small RNA have been identified, including piwi-interacting RNA (piRNA) and its subspecies repeat associated small interfering RNA (rasiRNA). (wikipedia.org)
  • While RNA silencing is an evolving class of mechanisms, a common theme is the fundamental relationship between small RNAs and gene expression. (wikipedia.org)
  • CDGS involves the assembly of small RNA complexes on nascent transcripts and is regarded as encompassing mechanisms of action which implicate transcriptional gene silencing (TGS) and co-transcriptional gene silencing (CTGS) events. (wikipedia.org)
  • This is significant at least because the evidence suggests that small RNAs play a role in the modulation of chromatin structure and TGS. (wikipedia.org)
  • lentiviral
  • Gammaretroviral and lentiviral vectors have so far been used in more than 300 clinical trials, addressing treatment options for various diseases. (wikipedia.org)
  • When similar ddRNAi constructs were delivered intrathecally using a lentiviral vector, pain relief in a neuropathic-rat model was demonstrated. (wikipedia.org)
  • expression
  • Upregulation by gene over-expression or down-regulation by gene inactivation of nitric oxide synthase has generated quantitative changes in abundance thereby permitting functional insights. (springer.com)
  • Although some tentative positive answers were given,nobody would say with certainty that RNA of various kinds was a truly promising means of altering gene expression. (ebooks.com)
  • HBx inhibits CYP2E1 gene expression via downregulating HNF4? (jove.com)
  • Together, HBx inhibits human CYP2E1 gene expression via downregulating HNF4? (jove.com)
  • Adenovirus and adeno-associated virus-mediated delivery of human myophosphorylase cDNA and LacZ cDNA to muscle in the ovine model of McArdle's disease: Expression and reexpression of glycogen phosphorylase. (fitness-vip.com)
  • Evidence of multiyear factor IX expression by AAV-mediated gene transfer to skeletal muscle in an individual with severe hemophilia B. Mol Ther 14, 452-455. (fitness-vip.com)
  • Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. (wikipedia.org)
  • When genes are silenced, their expression is reduced. (wikipedia.org)
  • In addition, they provide a more complete view on the development of diseases since diseases are generally associated with genes that have a reduced expression. (wikipedia.org)
  • RNA silencing or RNA interference refers to a family of gene silencing effects by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. (wikipedia.org)
  • However, the varied and nuanced role of RNA silencing in the regulation of gene expression remains an ongoing scientific inquiry. (wikipedia.org)
  • They have been used as hosts for gene expression. (wikipedia.org)
  • mutants
  • However, the recurrence of viremia after cessation of therapy and the development of escape mutants with prolonged treatment remain major obstacles in achieving complete cure. (natap.org)
  • however, these treatments have some drawbacks, including possible serious side effects in the case of interferon or recurrence of viremia after cessation of therapy and development of escape mutants after a long period of lamivudine treatment. (natap.org)
  • CRISPR
  • The first description of what would later be called CRISPR was from Osaka University researcher Yoshizumi Ishino in 1987, who accidentally cloned part of a CRISPR together with the iap gene, the target of interest. (wikipedia.org)
  • A major addition to the understanding of CRISPR came with Jansen's observation that the prokaryote repeat cluster was accompanied by a set of homologous genes that make up CRISPR-associated systems or cas genes. (wikipedia.org)
  • replicative
  • There are additional accessory genes depending on the virus (e.g., for HIV-1: vif, vpr, vpu, nef) whose products are involved in regulation of synthesis and processing viral RNA and other replicative functions. (wikipedia.org)
  • tissues
  • However, these strategies are either invasive or the methods may not be suitable for effective delivery of the gene throughout pulmonary tissues. (redorbit.com)
  • sequence
  • Researcher Yoshizumi Ishino and colleagues published their findings on the sequence of a gene called "iap" and its relation to E. coli. (wikipedia.org)