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An intranasally delivered ultra-conserved siRNA prophylactically represses SARS-CoV-2 infection in the lung and nasal cavity.
Idris, Adi; Supramaniam, Aroon; Tayyar, Yaman; Kelly, Gabrielle; McMillan, Nigel A J; Morris, Kevin V.
Afiliación
  • Idris A; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia; Centre for Immunlogy and Infection Control, School of Biomedical Sciences, Queensland University of Technology, K
  • Supramaniam A; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia.
  • Tayyar Y; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia; Prorenata Biotech, Molendinar, Queensland, Australia.
  • Kelly G; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia.
  • McMillan NAJ; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia.
  • Morris KV; Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia; School of Pharmacy and Medical Science, Griffith University, Southport, Queensland, Australia; Centre for Genomics and Personalized Health, School of Biomedical Sciences, Queensland University of Technology,
Antiviral Res ; 222: 105815, 2024 02.
Article en En | MEDLINE | ID: mdl-38246206
ABSTRACT
There remains a striking overall mortality burden of COVID-19 worldwide. Given the waning effectiveness of current SARS-CoV-2 antivirals due to the rapid emergence of new variants of concern (VOC), we employed a direct-acting molecular therapy approach using gene silencing RNA interference (RNAi) technology. In this study, we developed and screened several ultra-conserved small-interfering RNAs (siRNAs) before selecting one potent siRNA candidate for pre-clinical in vivo testing. This non-immunostimulatory, anti-SARS-CoV-2 siRNA candidate maintains its antiviral activity against all tested SARS-CoV-2 VOC and works effectively as a single agent. For the first time, significant antiviral effects in both the lungs and nasal cavities of SARS-CoV-2 infected mice were observed when this siRNA candidate was delivered intranasally (IN) as a prophylactic agent with the aid of lipid nanoparticles (LNPs). Importantly, a pre-exposure prophylactic IN-delivered anti-SARS-CoV-2 siRNA antiviral that can ameliorate viral replication in the nasal cavity could potentially prevent aerosol spread of respiratory viruses. An IN delivery approach would allow for the development of a direct-acting nasal spray approach that could be self-administered prophylactically.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Límite: Animals Idioma: En Revista: Antiviral Res Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: COVID-19 Límite: Animals Idioma: En Revista: Antiviral Res Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos