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

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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
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2021
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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 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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Molecular Therapy

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© 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.

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This publication has been entered as an advanced online version in Griffith Research Online.

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Subject

Biological sciences

Biomedical and clinical sciences

Genetics

Clinical sciences

Medical biotechnology

COVID-19

Coronavirus

LNP

RNAi

SARS-CoV-2

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Idris, A; Davis, A; Supramaniam, A; Acharya, D; Kelly, G; Tayyar, Y; West, N; Zhang, P; McMillan, CLD; Soemardy, C; Ray, R; O'Meally, D; Scott, TA; McMillan, NAJ; Morris, KV, A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19, Molecular Therapy, 2021

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