Key result
Pseudoknot-targeting Cas13b reduces SARS-CoV-2 viral replication by ~99% in infected mice.
Its licence doesn't allow us to show a copy here.
Why the study?
CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against SARS-CoV-2 variants, but effective targeting sites and therapeutic efficacy require investigation.
Does pseudoknot-targeting Cas13b reduce viral replication in SARS-CoV-2 infection models?
Does pseudoknot-targeting Cas13b reduce viral replication in SARS-CoV-2 infection models?
Effect estimate: 99% reduction
Pseudoknot-targeting Cas13b effectively suppresses SARS-CoV-2 replication in vitro and in hACE2 transgenic mice, offering a potential therapeutic strategy for RNA viruses.
Hypothesis-generating for Cas13 antivirals in models; leaves open clinical translation for SARS-CoV-2.
CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.
No takes yet. Share an insight, caveat, or question.
Yu et al. (2023) studied SARS-CoV-2 infection. Pseudoknot-targeting Cas13b was evaluated on Viral replication and viral titers (99% reduction). Pseudoknot-targeting Cas13b attenuated SARS-CoV-2 viral replication by 99% and significantly reduced viral titers in infected hACE2 transgenic mice.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: