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A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19.
Idris, Adi; Davis, Alicia; Supramaniam, Aroon; Acharya, Dhruba; Kelly, Gabrielle; Tayyar, Yaman; West, Nic; Zhang, Ping; McMillan, Christopher L D; Soemardy, Citradewi; Ray, Roslyn; O'Meally, Denis; Scott, Tristan A; McMillan, Nigel A J; Morris, Kevin V.
  • Idris A; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • Davis A; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA; Irell & Manella Graduate School of Biological Sciences at the City of Hope, Duarte, CA 91010, USA
  • Supramaniam A; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • Acharya D; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • Kelly G; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • Tayyar Y; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • West N; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • Zhang P; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia.
  • McMillan CLD; School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
  • Soemardy C; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA.
  • Ray R; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA.
  • O'Meally D; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA.
  • Scott TA; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA.
  • McMillan NAJ; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia. Electronic address: n.mcmillan@griffith.edu.au.
  • Morris KV; Menzies Health Institute Queensland, School of Medical Science Griffith University, Gold Coast Campus, QLD 4222, Australia; Center for Gene Therapy, Hematological Malignancy and Stem Cell Transplantation Institute at the City of Hope and City of Hope Beckman Research Institute, 1500 E. Duarte Road,
Mol Ther ; 29(7): 2219-2226, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1228174
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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 small interfering RNA (siRNA) therapeutic against SARS-CoV-2 infection using a novel lipid nanoparticle (LNP) delivery system. Multiple siRNAs targeting highly conserved regions of the SARS-CoV-2 virus were screened, and three candidate siRNAs emerged that effectively inhibit the virus by greater than 90% either alone or in combination with one another. We simultaneously developed and screened two novel LNP 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Double-Stranded / Drug Delivery Systems / RNA, Small Interfering / Nanoparticles / SARS-CoV-2 / COVID-19 Drug Treatment / Lipids Type of study: Prognostic study Topics: Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2021 Document Type: Article Affiliation country: J.ymthe.2021.05.004

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Full text: Available Collection: International databases Database: MEDLINE Main subject: RNA, Double-Stranded / Drug Delivery Systems / RNA, Small Interfering / Nanoparticles / SARS-CoV-2 / COVID-19 Drug Treatment / Lipids Type of study: Prognostic study Topics: Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Mol Ther Journal subject: Molecular Biology / Therapeutics Year: 2021 Document Type: Article Affiliation country: J.ymthe.2021.05.004