A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19.
Mol Ther
; 29(7): 2219-2226, 2021 07 07.
Article
in English
| MEDLINE | ID: covidwho-1228174
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
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.
Keywords
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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