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Annual Review of Entomology Jan 2020The RNA interference (RNAi) triggered by short/small interfering RNA (siRNA) was discovered in nematodes and found to function in most living organisms. RNAi has been... (Review)
Review
The RNA interference (RNAi) triggered by short/small interfering RNA (siRNA) was discovered in nematodes and found to function in most living organisms. RNAi has been widely used as a research tool to study gene functions and has shown great potential for the development of novel pest management strategies. RNAi is highly efficient and systemic in coleopterans but highly variable or inefficient in many other insects. Differences in double-stranded RNA (dsRNA) degradation, cellular uptake, inter- and intracellular transports, processing of dsRNA to siRNA, and RNA-induced silencing complex formation influence RNAi efficiency. The basic dsRNA delivery methods include microinjection, feeding, and soaking. To improve dsRNA delivery, various new technologies, including cationic liposome-assisted, nanoparticle-enabled, symbiont-mediated, and plant-mediated deliveries, have been developed. Major challenges to widespread use of RNAi in insect pest management include variable RNAi efficiency among insects, lack of reliable dsRNA delivery methods, off-target and nontarget effects, and potential development of resistance in insect populations.
Topics: Animals; Genetic Techniques; Insecta; RNA Interference
PubMed: 31610134
DOI: 10.1146/annurev-ento-011019-025224 -
Methods in Molecular Biology (Clifton,... 2018RNA interference (RNAi) is a biological process by which double-stranded RNA (dsRNA) induces sequence-specific gene silencing by targeting mRNA for degradation. As a... (Review)
Review
RNA interference (RNAi) is a biological process by which double-stranded RNA (dsRNA) induces sequence-specific gene silencing by targeting mRNA for degradation. As a tool for knocking down the expression of individual genes posttranscriptionally, RNAi has been widely used to study the cellular function of genes. In this chapter, I describe procedures for using gene-specific, synthetic, short interfering RNA (siRNA) to induce gene silencing in mammalian cells. Protocols for using lipid-based transfection reagents and electroporation techniques are provided. Potential challenges and problems associated with the siRNA technology are also discussed.
Topics: Animals; Electroporation; Gene Knockdown Techniques; Humans; RNA Interference; RNA Stability; Transfection
PubMed: 29423805
DOI: 10.1007/978-1-4939-7471-9_16 -
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 -
Nature Biotechnology Mar 2024Two decades of research on RNA interference (RNAi) have transformed a breakthrough discovery in biology into a robust platform for a new class of medicines that modulate... (Review)
Review
Two decades of research on RNA interference (RNAi) have transformed a breakthrough discovery in biology into a robust platform for a new class of medicines that modulate mRNA expression. Here we provide an overview of the trajectory of small-interfering RNA (siRNA) drug development, including the first approval in 2018 of a liver-targeted siRNA interference (RNAi) therapeutic in lipid nanoparticles and subsequent approvals of five more RNAi drugs, which used metabolically stable siRNAs combined with N-acetylgalactosamine ligands for conjugate-based liver delivery. We also consider the remaining challenges in the field, such as delivery to muscle, brain and other extrahepatic organs. Today's RNAi therapeutics exhibit high specificity, potency and durability, and are transitioning from applications in rare diseases to widespread, chronic conditions.
Topics: RNA Interference; RNA, Small Interfering; Liver; Acetylgalactosamine
PubMed: 38409587
DOI: 10.1038/s41587-023-02105-y -
Viruses Feb 2022Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily... (Review)
Review
Multiple antiviral immunities were developed to defend against viral infection in hosts. RNA interference (RNAi)-based antiviral innate immunity is evolutionarily conserved in eukaryotes and plays a vital role against all types of viruses. During the arms race between the host and virus, many viruses evolve viral suppressors of RNA silencing (VSRs) to inhibit antiviral innate immunity. Here, we reviewed the mechanism at different stages in RNAi-based antiviral innate immunity in plants and the counteractions of various VSRs, mainly upon infection of RNA viruses in model plant Arabidopsis. Some critical challenges in the field were also proposed, and we think that further elucidating conserved antiviral innate immunity may convey a broad spectrum of antiviral strategies to prevent viral diseases in the future.
Topics: Arabidopsis; Host-Pathogen Interactions; Immunity, Innate; Plant Diseases; Plant Immunity; RNA Interference; RNA Virus Infections
PubMed: 35216025
DOI: 10.3390/v14020432 -
Nature Cell Biology Dec 2022The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the...
The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function. Induced by ER stress, ERAS is mediated by the Argonaute protein RDE-1/AGO2, is conserved in mammals and promotes ER-associated RNA turnover. ERAS and ERAD are complementary, as simultaneous inactivation of both quality-control pathways leads to increased ER stress, reduced protein quality control and impaired intestinal integrity. Collectively, our findings indicate that ER homeostasis and organismal health are protected by synergistic functions of ERAS and ERAD.
Topics: RNA Interference; Endoplasmic Reticulum
PubMed: 36471127
DOI: 10.1038/s41556-022-01025-4 -
Nature Reviews. Immunology Jan 2019Protection against microbial infection in eukaryotes is provided by diverse cellular and molecular mechanisms. Here, we present a comparative view of the antiviral... (Review)
Review
Protection against microbial infection in eukaryotes is provided by diverse cellular and molecular mechanisms. Here, we present a comparative view of the antiviral activity of virus-derived small interfering RNAs in fungi, plants, invertebrates and mammals, detailing the mechanisms for their production, amplification and activity. We also highlight the recent discovery of viral PIWI-interacting RNAs in animals and a new role for mobile host and pathogen small RNAs in plant defence against eukaryotic pathogens. In turn, viruses that infect plants, insects and mammals, as well as eukaryotic pathogens of plants, have evolved specific virulence proteins that suppress RNA interference (RNAi). Together, these advances suggest that an antimicrobial function of the RNAi pathway is conserved across eukaryotic kingdoms.
Topics: Animals; Anti-Infective Agents; Eukaryotic Cells; Host-Pathogen Interactions; Humans; Mammals; Plants; RNA Interference; RNA, Small Interfering
PubMed: 30301972
DOI: 10.1038/s41577-018-0071-x -
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 -
Nature Oct 2019
Topics: Clinical Trials as Topic; Genetic Diseases, Inborn; Genetic Therapy; Humans; RNA; RNA Interference
PubMed: 31619808
DOI: 10.1038/d41586-019-03067-5 -
Annual Review of Pharmacology and... Jan 2017Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology,... (Review)
Review
Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.
Topics: Animals; Autoimmune Diseases; Cardiovascular Diseases; Humans; Oligonucleotides, Antisense; RNA Interference; RNA Splicing
PubMed: 27732800
DOI: 10.1146/annurev-pharmtox-010716-104846