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      A review on current status of antiviral siRNA

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          Summary

          Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene‐silencing phenomenon in which sequence‐specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.

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          Knocking down barriers: advances in siRNA delivery

          Key Points RNA interference (RNAi) is a fundamental pathway in eukaryotic cells by which sequence-specific small interfering RNA (siRNA) is able to silence genes through the destruction of complementary mRNA. RNAi is an important therapeutic tool that can be used to silence aberrant endogenous genes or to knockdown genes essential to the proliferation of infectious organisms. Delivery remains the central challenge to the therapeutic application of RNAi technology. Before siRNA can take effect in the cytoplasm of a target cell, it must be transported through the body to the target site without undergoing clearance or degradation. Currently, the most effective synthetic, non-viral delivery agents of siRNA are lipids, lipid-like materials and polymers. Various cationic agents including stable nucleic acid–lipid particles, lipidoids, cyclodextrin polymers and polyethyleneimine polymers have been used to achieve the successful systemic delivery of siRNA in mammals without inducing significant toxicity. Direct conjugation of delivery agents to siRNA can facilitate delivery. For example, cholesterol-modified siRNA enables targeting to the liver. RNAi therapeutics have progressed to the clinic, where studies are being conducted to determine siRNA efficacy in treating several diseases, including age-related macular degeneration and respiratory syncytial virus. Moving forward, it will be important to pay close attention to the potential nonspecific immunostimulatory effects of siRNA. Modifications to siRNA can be used to minimize stimulation of the immune system, and an increased emphasis must be placed on performing proper controls to ensure that therapeutic effects are sequence-specific.
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            Ribo-gnome: the big world of small RNAs.

            Small RNA guides--microRNAs, small interfering RNAs, and repeat-associated small interfering RNAs, 21 to 30 nucleotides in length--shape diverse cellular pathways, from chromosome architecture to stem cell maintenance. Fifteen years after the discovery of RNA silencing, we are only just beginning to understand the depth and complexity of how these RNAs regulate gene expression and to consider their role in shaping the evolutionary history of higher eukaryotes.
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              A cellular microRNA mediates antiviral defense in human cells.

              In eukaryotes, 21- to 24-nucleotide-long RNAs engage in sequence-specific interactions that inhibit gene expression by RNA silencing. This process has regulatory roles involving microRNAs and, in plants and insects, it also forms the basis of a defense mechanism directed by small interfering RNAs that derive from replicative or integrated viral genomes. We show that a cellular microRNA effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (PFV-1) in human cells. PFV-1 also encodes a protein, Tas, that suppresses microRNA-directed functions in mammalian cells and displays cross-kingdom antisilencing activities. Therefore, through fortuitous recognition of foreign nucleic acids, cellular microRNAs have direct antiviral effects in addition to their regulatory functions.
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                Author and article information

                Contributors
                abid.qureshi@skims.ac.in
                Journal
                Rev Med Virol
                Rev. Med. Virol
                10.1002/(ISSN)1099-1654
                RMV
                Reviews in Medical Virology
                John Wiley and Sons Inc. (Hoboken )
                1052-9276
                1099-1654
                15 April 2018
                July 2018
                : 28
                : 4 ( doiID: 10.1002/rmv.v28.4 )
                : e1976
                Affiliations
                [ 1 ] Biomedical Informatics Center Sher‐i‐Kashmir Institute of Medical Sciences (SKIMS) Srinagar India
                Author notes
                [*] [* ] Correspondence

                Abid Qureshi, Biomedical Informatics Center, Sher‐i‐Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar, Jammu and Kashmir 190011, India.

                Email: abid.qureshi@ 123456skims.ac.in

                Author information
                http://orcid.org/0000-0002-1140-1649
                Article
                RMV1976 RMV-2017-052.R1
                10.1002/rmv.1976
                7169094
                29656441
                cb575c73-0d7c-491e-9cca-099ad6620103
                Copyright © 2018 John Wiley & Sons, Ltd.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 03 November 2017
                : 18 January 2018
                : 12 February 2018
                Page count
                Figures: 4, Tables: 2, Pages: 11, Words: 3873
                Funding
                Funded by: Indian Council of Medical Research (ICMR) , open-funder-registry 10.13039/501100001411;
                Funded by: Sher‐i‐Kashmir Institute of Medical Sciences (SKIMS)
                Funded by: Biomedical Informatics Center
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                July 2018
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

                Microbiology & Virology
                antiviral,clinical trials,delivery,design,limitations,resources,rnai,sirna,virus
                Microbiology & Virology
                antiviral, clinical trials, delivery, design, limitations, resources, rnai, sirna, virus

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