美国佐治亚理工学院Philip J. Santangelo、Chiara Zurla等研究人员合作发现，mRNA编码的Cas13a可在啮齿动物中治疗流感和SARS-CoV-2感染。相关论文于2021年2月3日在线发表于国际学术期刊《自然—生物技术》。

研究人员使用信使RNA（mRNA）编码的Cas13a分别减轻了小鼠和仓鼠中的甲型流感病毒和SARS-CoV-2感染。研究人员设计了特异性针对流感病毒PB1和PB2高度保守区域、SARS-CoV-2的复制酶和核衣壳基因的CRISPR RNA（crRNA），并选择了在细胞培养中最有效降低病毒RNA水平的crRNA。

研究人员使用雾化器将聚合物包裹的Cas13a mRNA和经过验证向导RNA递送至呼吸道。在小鼠中，Cas13a在感染后递送时可有效降解肺组织中的流感RNA，而在仓鼠中，Cas13a递送可减少SARS-CoV-2复制并减轻症状。这些发现表明，Cas13a介导的致病性病毒靶向可以减轻呼吸道感染。

据介绍，Cas13a已用于在细胞培养中靶向RNA病毒，但尚未在动物模型中证明其功效。

附：英文原文

Title: Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents

Author: Emmeline L. Blanchard, Daryll Vanover, Swapnil Subhash Bawage, Pooja Munnilal Tiwari, Laura Rotolo, Jared Beyersdorf, Hannah E. Peck, Nicholas C. Bruno, Robert Hincapie, Frank Michel, Jackelyn Murray, Heena Sadhwani, Bob Vanderheyden, M. G. Finn, Margo A. Brinton, Eric R. Lafontaine, Robert J. Hogan, Chiara Zurla, Philip J. Santangelo

Issue&Volume: 2021-02-03

Abstract: Cas13a has been used to target RNA viruses in cell culture, but efficacy has not been demonstrated in animal models. In this study, we used messenger RNA (mRNA)-encoded Cas13a for mitigating influenza virus A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in mice and hamsters, respectively. We designed CRISPR RNAs (crRNAs) specific for PB1 and highly conserved regions of PB2 of influenza virus, and against the replicase and nucleocapsid genes of SARS-CoV-2, and selected the crRNAs that reduced viral RNA levels most efficiently in cell culture. We delivered polymer-formulated Cas13a mRNA and the validated guides to the respiratory tract using a nebulizer. In mice, Cas13a degraded influenza RNA in lung tissue efficiently when delivered after infection, whereas in hamsters, Cas13a delivery reduced SARS-CoV-2 replication and reduced symptoms. Our findings suggest that Cas13a-mediated targeting of pathogenic viruses can mitigate respiratory infections. Cas13a delivered to the lung of mice and hamsters inhibits replication of influenza virus and SARS-CoV-2.

DOI: 10.1038/s41587-021-00822-w

Source: https://www.nature.com/articles/s41587-021-00822-w