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Microbiology and Molecular Biology... Dec 2003Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a... (Review)
Review
Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA. The resulting phenotypes either are identical to those of genetic null mutants or resemble an allelic series of mutants. Specific gene silencing has been shown to be related to two ancient processes, cosuppression in plants and quelling in fungi, and has also been associated with regulatory processes such as transposon silencing, antiviral defense mechanisms, gene regulation, and chromosomal modification. Extensive genetic and biochemical analysis revealed a two-step mechanism of RNAi-induced gene silencing. The first step involves degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like activity. In the second step, the siRNAs join an RNase complex, RISC (RNA-induced silencing complex), which acts on the cognate mRNA and degrades it. Several key components such as Dicer, RNA-dependent RNA polymerase, helicases, and dsRNA endonucleases have been identified in different organisms for their roles in RNAi. Some of these components also control the development of many organisms by processing many noncoding RNAs, called micro-RNAs. The biogenesis and function of micro-RNAs resemble RNAi activities to a large extent. Recent studies indicate that in the context of RNAi, the genome also undergoes alterations in the form of DNA methylation, heterochromatin formation, and programmed DNA elimination. As a result of these changes, the silencing effect of gene functions is exercised as tightly as possible. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes.
Topics: Animals; Humans; RNA Interference; RNA, Double-Stranded; RNA, Small Interfering
PubMed: 14665679
DOI: 10.1128/MMBR.67.4.657-685.2003 -
Current Opinion in Immunology Oct 2018Infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide... (Review)
Review
Infection of plants and insects with RNA and DNA viruses triggers Dicer-dependent production of virus-derived small interfering RNAs (vsiRNAs), which subsequently guide specific virus clearance by RNA interference (RNAi). Consistent with a major antiviral function of RNAi, productive virus infection in these eukaryotic hosts depends on the expression of virus-encoded suppressors of RNAi (VSRs). The eukaryotic RNAi pathway is highly conserved, particularly between insects and mammals. This review will discuss key recent findings that indicate a natural antiviral function of the RNAi pathway in mammalian cells. We will summarize the properties of the characterized mammalian vsiRNAs and VSRs and highlight important questions remaining to be addressed on the function and mechanism of mammalian antiviral RNAi.
Topics: Animals; Humans; Mammals; Protective Agents; RNA Interference; RNA, Viral; Virus Diseases; Viruses
PubMed: 30015086
DOI: 10.1016/j.coi.2018.06.010 -
Trends in Genetics : TIG Jun 2008The discovery of RNA interference (RNAi), the process of sequence-specific gene silencing initiated by double-stranded RNA (dsRNA), has broadened our understanding of... (Review)
Review
The discovery of RNA interference (RNAi), the process of sequence-specific gene silencing initiated by double-stranded RNA (dsRNA), has broadened our understanding of gene regulation and has revolutionized methods for genetic analysis. A remarkable property of RNAi in the nematode Caenorhabditis elegans and in some other multicellular organisms is its systemic nature: silencing signals can cross cellular boundaries and spread between cells and tissues. Furthermore, C. elegans and some other organisms can also perform environmental RNAi: sequence-specific gene silencing in response to environmentally encountered dsRNA. This phenomenon has facilitated significant technological advances in diverse fields including functional genomics and agricultural pest control. Here, we describe the characterization and current understanding of environmental RNAi and discuss its potential applications.
Topics: Animals; Caenorhabditis elegans; Environment; Gene Silencing; Models, Biological; RNA Interference; RNA Transport
PubMed: 18450316
DOI: 10.1016/j.tig.2008.03.007 -
BMJ (Clinical Research Ed.) May 2004
Review
Topics: Animals; Gene Transfer Techniques; Genetic Therapy; Genome, Viral; Humans; RNA Interference; Virus Diseases
PubMed: 15155505
DOI: 10.1136/bmj.328.7450.1245 -
Pharmacogenomics Jan 2005
Review
Topics: Animals; Gene Targeting; Genetic Therapy; Humans; RNA Interference
PubMed: 15723601
DOI: 10.1517/14622416.6.1.13 -
Annual Review of Phytopathology Aug 2018The origin of RNA interference (RNAi), the cell sentinel system widely shared among eukaryotes that recognizes RNAs and specifically degrades or prevents their... (Review)
Review
The origin of RNA interference (RNAi), the cell sentinel system widely shared among eukaryotes that recognizes RNAs and specifically degrades or prevents their translation in cells, is suggested to predate the last eukaryote common ancestor ( 138 ). Of particular relevance to plant pathology is that in plants, but also in some fungi, insects, and lower eukaryotes, RNAi is a primary and effective antiviral defense, and recent studies have revealed that small RNAs (sRNAs) involved in RNAi play important roles in other plant diseases, including those caused by cellular plant pathogens. Because of this, and because RNAi can be manipulated to interfere with the expression of endogenous genes in an intra- or interspecific manner, RNAi has been used as a tool in studies of gene function but also for plant protection. Here, we review the discovery of RNAi, canonical mechanisms, experimental and translational applications, and new RNA-based technologies of importance to plant pathology.
Topics: Plant Diseases; Plant Pathology; RNA Interference
PubMed: 29979927
DOI: 10.1146/annurev-phyto-080417-050044 -
The EMBO Journal Nov 2023RNA-based therapeutics have the potential to revolutionize the treatment and prevention of human diseases. While early research faced setbacks, it established the basis... (Review)
Review
RNA-based therapeutics have the potential to revolutionize the treatment and prevention of human diseases. While early research faced setbacks, it established the basis for breakthroughs in RNA-based drug design that culminated in the extraordinarily fast development of mRNA vaccines to combat the COVID-19 pandemic. We have now reached a pivotal moment where RNA medicines are poised to make a broad impact in the clinic. In this review, we present an overview of different RNA-based strategies to generate novel therapeutics, including antisense and RNAi-based mechanisms, mRNA-based approaches, and CRISPR-Cas-mediated genome editing. Using three rare genetic diseases as examples, we highlight the opportunities, but also the challenges to wide-ranging applications of this class of drugs.
Topics: Humans; RNA; Pandemics; Gene Editing; RNA Interference; Genetic Therapy
PubMed: 37728251
DOI: 10.15252/embj.2023114760 -
Annual Review of Pharmacology and... 2016A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi... (Review)
Review
A resurgence in clinical trials using RNA interference (RNAi) occurred in 2012. Although there were initial difficulties in achieving efficacious results with RNAi without toxic side effects, advances in delivery and improved chemistry made this resurgence possible. More than 20 RNAi-based therapeutics are currently in clinical trials, and several of these are Phase III trials. Continued positive results from these trials have helped bolster further attempts to develop clinically relevant RNAi therapies. With a wide variety of disease targets to choose from, the first RNAi therapeutic to be clinically approved is not far off. This review covers recently established and completed clinical trials.
Topics: Clinical Trials as Topic; Drug Delivery Systems; Humans; Pharmaceutical Preparations; RNA Interference
PubMed: 26738473
DOI: 10.1146/annurev-pharmtox-010715-103633 -
Advanced Drug Delivery Reviews Sep 2017Since the approval of bevacizumab as anti-angiogenic therapy in 2004 by the FDA, an array of angiogenesis inhibitors have been developed and approved. However, results... (Review)
Review
Since the approval of bevacizumab as anti-angiogenic therapy in 2004 by the FDA, an array of angiogenesis inhibitors have been developed and approved. However, results were disappointing with regard to their therapeutic efficacy. RNA interference approaches offer the possibility of rational design with high specificity, lacking in many current drug treatments for various diseases including cancer. However, in vivo delivery issues still represent a significant obstacle for widespread clinical applications. In the current review, we summarize the advances in the last decade in the field of angiogenesis-targeted RNA interference approaches, with special emphasis on oncology applications. We present pro-angiogenic and anti-angiogenic factors as potential targets, experimental evidence and clinical trials data on angiogenesis regulation by RNA interference. Consequent challenges and opportunities are discussed.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Neovascularization, Pathologic; RNA Interference
PubMed: 28163106
DOI: 10.1016/j.addr.2017.01.008 -
Journal of Cellular Physiology Nov 2010RNA interference, a recently discovered new mechanism controlling gene expression via small RNAs, was shown to be involved in characterization and control of basic... (Review)
Review
RNA interference, a recently discovered new mechanism controlling gene expression via small RNAs, was shown to be involved in characterization and control of basic ovarian cell functions. The main classes of small RNAs, as well as their expression in ovaries have been described. Furthermore, the successful application of RNA interference for study and control of basic ovarian functions (proliferation, apoptosis, secretory activity, luteogenesis, oocyte maturation, and related ovarian cell malignant transformation) and production of recombinant proteins have been demonstrated. Application of RNA interference in reproductive biology and medicine can be successful in two main areas: (1) characterization and prediction of physiological and pathological state (association between particular small RNA and physiological or pathological processes), (2) application of small RNAs for regulation of reproductive processes and treatment of reproductive disorders or their particular indexes. Problems of improvement of small RNA delivery to target ovarian cells and potent RNA interference-related approaches for treatment of ovarian disorders (especially of ovarian cancer) have been discussed.
Topics: Animals; Female; Infertility, Female; Oocytes; Ovary; RNA Interference; Reproduction
PubMed: 20568223
DOI: 10.1002/jcp.22277