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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 -
Discovery Medicine Feb 2013Despite billions of dollars allocated to cancer research, cancer remains the number 2 cause of death in the United States with less than 50% of advanced cancer patients... (Review)
Review
Despite billions of dollars allocated to cancer research, cancer remains the number 2 cause of death in the United States with less than 50% of advanced cancer patients living one year following standard treatment. Cancer is a complex disease both intrinsically and in relation to its host environment. From a molecular standpoint no two cancers are the same despite histotypic similarity. As evidenced by the recent advances in molecular biology, treatment for advanced cancer is headed towards specific targeting of vulnerable signaling nodes within the reconfigured pathways created by "omic" rewiring. With advancements in proteo-genomics and the capacity of bioinformatics, complex tumor biology can now be more effectively and rapidly analyzed to discover the vulnerable high information transfer nodes within individual tumors. RNA interference (RNAi) technology, with its capability to knock down the expression of targeted genes (the vulnerable nodes), is moving into the clinic to target these nodes, which are integral to tumor maintenance, with a low risk of side-effects and to block intrinsic immunosuppressors thereby priming the tumor for immune attack. An RNAi based sequential approach, a so called "one-two punch," is being advocated comprising tumor volume reduction (ideally to minimal residual disease status) effected by integrated multi-target knockdown followed by immune activation. Examples and recent developments are provided to illustrate this highly powerful approach heralding the future of personalized cancer therapy.
Topics: Clinical Trials as Topic; Humans; Neoplasms; Precision Medicine; RNA Interference
PubMed: 23449112
DOI: No ID Found -
The Plant Cell Aug 2022Host-induced gene silencing (HIGS) refers to the silencing of genes in pathogens and pests by expressing homologous double-stranded RNAs (dsRNA) or artificial microRNAs... (Review)
Review
Host-induced gene silencing (HIGS) refers to the silencing of genes in pathogens and pests by expressing homologous double-stranded RNAs (dsRNA) or artificial microRNAs (amiRNAs) in the host plant. The discovery of such trans-kingdom RNA silencing has enabled the development of RNA interference-based approaches for controlling diverse crop pathogens and pests. Although HIGS is a promising strategy, the mechanisms by which these regulatory RNAs translocate from plants to pathogens, and how they induce gene silencing in pathogens, are poorly understood. This lack of understanding has led to large variability in the efficacy of various HIGS treatments. This variability is likely due to multiple factors, such as the ability of the target pathogen or pest to take up and/or process RNA from the host, the specific genes and target sequences selected in the pathogen or pest for silencing, and where, when, and how the dsRNAs or amiRNAs are produced and translocated. In this review, we summarize what is currently known about the molecular mechanisms underlying HIGS, identify key unanswered questions, and explore strategies for improving the efficacy and reproducibility of HIGS treatments in the control of crop diseases.
Topics: Gene Silencing; Plant Diseases; Plants; RNA Interference; RNA, Double-Stranded; Reproducibility of Results
PubMed: 35666177
DOI: 10.1093/plcell/koac165 -
Current Issues in Molecular Biology Jan 2005RNA interference (RNAi) is the sequence-specific gene silencing induced by double-stranded RNA. RNAi is mediated by 21-23 nucleotide small interfering RNAs (siRNAs)... (Review)
Review
RNA interference (RNAi) is the sequence-specific gene silencing induced by double-stranded RNA. RNAi is mediated by 21-23 nucleotide small interfering RNAs (siRNAs) which are produced from long double-stranded RNAs by RNAse II-like enzyme Dicer. The resulting siRNAs are incorporated into a RNA-induced silencing complex (RISC) that targets and cleaves mRNA complementary to the siRNAs. Since its inception in 1998, RNAi has been demonstrated in organisms ranging from trypanosomes to nematodes to vertebrates. Potential uses already in progress include the examination of specific gene function in living systems, the development of anti-viral and anti-cancer therapies, and genome-wide screens. In this review, we discuss the landmark discoveries that established the contextual framework leading up to our current understanding of RNAi. We also provide an overview of current developments and future applications.
Topics: Animals; Communicable Diseases; Forecasting; Genes, Dominant; Genetic Diseases, Inborn; Humans; Molecular Biology; Neoplasms; RNA Interference; RNA, Small Interfering
PubMed: 15580776
DOI: No ID Found -
Cell Dec 2015Image-based screening is used to measure a variety of phenotypes in cells and whole organisms. Combined with perturbations such as RNA interference, small molecules, and... (Review)
Review
Image-based screening is used to measure a variety of phenotypes in cells and whole organisms. Combined with perturbations such as RNA interference, small molecules, and mutations, such screens are a powerful method for gaining systematic insights into biological processes. Screens have been applied to study diverse processes, such as protein-localization changes, cancer cell vulnerabilities, and complex organismal phenotypes. Recently, advances in imaging and image-analysis methodologies have accelerated large-scale perturbation screens. Here, we describe the state of the art for image-based screening experiments and delineate experimental approaches and image-analysis approaches as well as discussing challenges and future directions, including leveraging CRISPR/Cas9-mediated genome engineering.
Topics: CRISPR-Cas Systems; Cells; High-Throughput Screening Assays; Image Processing, Computer-Assisted; Microscopy; Proteins; RNA Interference
PubMed: 26638068
DOI: 10.1016/j.cell.2015.11.007 -
Pharmacology & Therapeutics Apr 2019Small-molecule and protein/antibody drugs mainly act on genome-derived proteins to exert pharmacological effects. RNA based therapies hold the promise to expand the... (Review)
Review
Small-molecule and protein/antibody drugs mainly act on genome-derived proteins to exert pharmacological effects. RNA based therapies hold the promise to expand the range of druggable targets from proteins to RNAs and the genome, as evidenced by several RNA drugs approved for clinical practice and many others under active trials. While chemo-engineered RNA mimics have found their success in marketed drugs and continue dominating basic research and drug development, these molecules are usually conjugated with extensive and various modifications. This makes them completely different from cellular RNAs transcribed from the genome that usually consist of unmodified ribonucleotides or just contain a few posttranscriptional modifications. The use of synthetic RNA mimics for RNA research and drug development is also in contrast with the ultimate success of protein research and therapy utilizing biologic or recombinant proteins produced and folded in living cells instead of polypeptides or proteins synthesized in vitro. Indeed, efforts have been made recently to develop RNA bioengineering technologies for cost-effective and large-scale production of biologic RNA molecules that may better capture the structures, functions, and safety profiles of natural RNAs. In this article, we provide an overview on RNA therapeutics for the treatment of human diseases via RNA interference mechanisms. By illustrating the structural differences between natural RNAs and chemo-engineered RNA mimics, we focus on discussion of a novel class of bioengineered/biologic RNA agents produced through fermentation and their potential applications to RNA research and drug development.
Topics: Animals; Bioengineering; Humans; RNA; RNA Interference
PubMed: 30521885
DOI: 10.1016/j.pharmthera.2018.11.011 -
Viruses Oct 2023Shrimp aquaculture has become a vital industry, meeting the growing global demand for seafood. Shrimp viral diseases have posed significant challenges to the aquaculture... (Review)
Review
Shrimp aquaculture has become a vital industry, meeting the growing global demand for seafood. Shrimp viral diseases have posed significant challenges to the aquaculture industry, causing major economic losses worldwide. Conventional treatment methods have proven to be ineffective in controlling these diseases. However, recent advances in RNA interference (RNAi) technology have opened new possibilities for combating shrimp viral diseases. This cutting-edge technology uses cellular machinery to silence specific viral genes, preventing viral replication and spread. Numerous studies have shown the effectiveness of RNAi-based therapies in various model organisms, paving the way for their use in shrimp health. By precisely targeting viral pathogens, RNAi has the potential to provide a sustainable and environmentally friendly solution to combat viral diseases in shrimp aquaculture. This review paper provides an overview of RNAi-based therapy and its potential as a game-changer for shrimp viral diseases. We discuss the principles of RNAi, its application in combating viral infections, and the current progress made in RNAi-based therapy for shrimp viral diseases. We also address the challenges and prospects of this innovative approach.
Topics: Animals; RNAi Therapeutics; RNA Interference; Virus Diseases; Crustacea; Aquaculture
PubMed: 37896827
DOI: 10.3390/v15102050 -
Blood Aug 2005RNA interference (RNAi) is a conserved biologic response to double-stranded RNA that results in the sequence-specific silencing of target gene expression. Over the past... (Review)
Review
RNA interference (RNAi) is a conserved biologic response to double-stranded RNA that results in the sequence-specific silencing of target gene expression. Over the past 5 years, an intensive research effort has facilitated the rapid movement of RNAi from a relatively obscure biologic phenomenon to a valuable tool used to silence target gene expression and perform large-scale functional genomic screens. In fact, recent studies reported in this journal and others have demonstrated success using RNAi to address the role of oncogene expression in leukemia cell lines and to validate the therapeutic potential of RNAi for treating these blood disorders. In order to advance these applications and gain an appreciation for the future of RNAi both in basic research and in the treatment of diseases caused by aberrant gene expression, it is important to have an understanding of the process of RNAi and its limitations.
Topics: Gene Expression Regulation, Neoplastic; Hematologic Neoplasms; Humans; RNA Interference; RNA, Small Interfering
PubMed: 15827131
DOI: 10.1182/blood-2004-12-4643 -
ELife Aug 2023Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target...
Loss-of-function genetic tools are widely applied for validating therapeutic targets, but their utility remains limited by incomplete on- and uncontrolled off-target effects. We describe artificial RNA interference (ARTi) based on synthetic, ultra-potent, off-target-free shRNAs that enable efficient and inducible suppression of any gene upon introduction of a synthetic target sequence into non-coding transcript regions. ARTi establishes a scalable loss-of-function tool with full control over on- and off-target effects.
Topics: RNA Interference; RNA, Small Interfering
PubMed: 37552050
DOI: 10.7554/eLife.84792 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Apr 2021RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the... (Review)
Review
RNA interference (RNAi) is one of the important mechanisms to regulate gene expression in eukaryotes. One of the original functions of RNAi is to facilitate the antiviral strategy of host. Early studies reveal that invertebrates can use RNAi to resist viruses. However, if this mechanism exists in mammals is still controversial. The latest studies confirm that mammals do have the RNAi-based immunity, and researchers believe that RNAi-based antiviral immunity is a brand-new immunological mechanism that was neglected in the past. It is worthy to note that virus can also use RNAi to enhance its infectivity and immune escape in host cells. This review introduces the research history of RNAi-based antiviral immunity in animals and summarizes the main findings in this field. Last but not least, we indicate a series of unresolved questions about RNAi-based antiviral immunity, and explore the relationship between RNAi-based antiviral immunity and other innate immunological pathways. The virus-mediated RNAi pathway in animal is not only an interesting basic biology question, but also has important guiding roles in the development of antiviral drugs.
Topics: Animals; Antiviral Agents; Immunity, Innate; Mammals; RNA Interference; RNA, Small Interfering; RNA, Viral
PubMed: 33973438
DOI: 10.13345/j.cjb.200665