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  • A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19

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    Idris492922-Accepted.pdf (4.168Mb)
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    Accepted Manuscript (AM)
    Author(s)
    Idris, Adi
    Davis, Alicia
    Supramaniam, Aroon
    Acharya, Dhruba
    Kelly, Gabrielle
    Tayyar, Yaman
    West, Nic
    Zhang, Ping
    McMillan, Christopher LD
    Soemardy, Citradewi
    Ray, Roslyn
    O'Meally, Denis
    Scott, Tristan A
    McMillan, Nigel AJ
    Morris, Kevin V
    Griffith University Author(s)
    Supramaniam, Aroon
    McMillan, Nigel
    Morris, Kevin V.
    Kelly, Gabrielle A.
    Idris, Adi
    Acharya, Dhruba
    Tayyar, Yaman
    West, Nic P.
    Zhang, Ping
    Year published
    2021
    Metadata
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    Abstract
    Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three candidate siRNAs emerged that effectively inhibit virus by greater than 90% either alone or in combination with one another. We ...
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    Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. Despite several emerging vaccines, there remains no verifiable therapeutic targeted specifically to the virus. Here we present a highly effective siRNA therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle delivery system. Multiple small-interfering RNAs (siRNAs) targeting highly conserved regions of the SARS-CoV-2 virus were screened and three candidate siRNAs emerged that effectively inhibit virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel lipid nanoparticle formulations for the delivery of these candidate siRNA therapeutics to the lungs, an organ that incurs immense damage during SARS-CoV-2 infection. Encapsulation of siRNAs in these LNPs followed by in vivo injection demonstrated robust repression of virus in the lungs and a pronounced survival advantage to the treated mice. Our LNP-siRNA approaches are scalable and can be administered upon the first sign of SARS-CoV-2 infection in humans. We suggest that an siRNA-LNP therapeutic approach could prove highly useful in treating COVID-19 disease as an adjunctive therapy to current vaccine strategies.
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    Journal Title
    Molecular Therapy
    DOI
    https://doi.org/10.1016/j.ymthe.2021.05.004
    Copyright Statement
    © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Note
    This publication has been entered as an advanced online version in Griffith Research Online.
    Subject
    Biological sciences
    Biomedical and clinical sciences
    COVID-19
    Coronavirus
    LNP
    RNAi
    SARS-CoV-2
    Publication URI
    http://hdl.handle.net/10072/404511
    Collection
    • Journal articles

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