Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza

被引：369

作者：

Abbott, Timothy R. ^{[1
]}

Dhamdhere, Girija ^{[2
]}

Liu, Yanxia ^{[1
]}

Lin, Xueqiu ^{[1
]}

Goudy, Laine ^{[1
]}

Zeng, Leiping ^{[1
]}

Chemparathy, Augustine ^{[3
]}

Chmura, Stephen ^{[4
]}

Heaton, Nicholas S. ^{[5
]}

Debs, Robert ^{[4
]}

Pande, Tara ^{[6
]}

Endy, Drew ^{[1
]}

La Russa, Marie F. ^{[1
]}

Lewis, David B. ^{[2
]}

Qi, Lei S. ^{[1
,7
,8
]}

机构：

[1] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Management Sci & Engn, Stanford, CA 94305 USA

[4] DNARx, San Francisco, CA 94107 USA

[5] Duke Univ, Dept Mol Genet & Microbiol, Sch Med, Durham, NC 27710 USA

[6] Los Altos High Sch, Los Altos, CA 94022 USA

[7] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA

[8] Stanford Univ, ChEM H, Stanford, CA 94305 USA

来源：

CELL | 2020年 / 181卷 / 04期

关键词：

VIRUS-RNA SEGMENTS; SARS-COV; MERS-COV; VACCINE; PROTEIN; RESERVOIRS; SEQUENCES; DELIVERY; ORIGIN;

D O I：

10.1016/j.cell.2020.04.020

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC -MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1 N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC -MAN has the potential to become an important pan-coronavirus inhibition strategy.

引用

页码：865 / +

页数：24

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