Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis.

ABSTRACT: Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen with over 16,000 RNAi triggers against the SARS-CoV-2 genome using a massively parallel assay to identify hyper-potent siRNAs. We selected 10 candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity with IC50<20pM and strong neutralisation in live virus experiments. We further enhanced the activity by combinatorial pairing of the siRNA candidates to develop siRNA cocktails and found that these cocktails are active against multiple types of variants of concern (VOC). We examined over 2,000 possible mutations to the siRNA target sites using saturation m

SUBMITTER: Yogev O 

PROVIDER: S-EPMC9016640 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature