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Gene Ther . Molecular targeting of vulnerable RNA sequences in SARS CoV-2: identifying clinical feasibility

tetano

Editor, Senior Moderator
Gene Ther


. 2020 Nov 12.
doi: 10.1038/s41434-020-00210-0. Online ahead of print.
Molecular targeting of vulnerable RNA sequences in SARS CoV-2: identifying clinical feasibility


G Ian Gallicano[SUP] 1 [/SUP], John L Casey[SUP] 2 [/SUP], Jiayu Fu[SUP] 3 [/SUP], Samiksha Mahapatra[SUP] 3 [/SUP]



Affiliations

Abstract

Covid-19 (SARS CoV-2) has become a deadly, world-wide pandemic. Although most who are infected survive, complications from the virus can be pronounced and long-lasting. To date, of all the respiratory viruses including influenza and coronaviruses, only influenza has had a drug (i.e., Tamiflu) specifically targeted to treat and prevent infection. As a result, additional agents that specifically target viral production and are clinically feasible are needed to alleviate respiratory viral infections. The idea of using a miRNA/siRNA molecular approach for treating various diseases was postulated over a decade ago; however, only within the past few years has it become feasible. One technological advancement has been the molecular linkage of lipophilic moieties to mi/siRNAs in order to bypass the need for enveloping these inhibitory RNAs in lipid-based transfection reagents, which could irritate the airway if inhaled. Here we show that siRNAs and miRNAs inhibit SARS CoV-2 spike protein production in a dose-dependent manner in both HEK293 cells and a primary human airway tracheal cell line. We also show that this inhibition is equally robust using a clinically relevant siRNA that does not need to be prepped with a transfection reagent.
 
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