VSV-CRISPR/CasRX对抗冠状病毒感染的作用和机制研究

2019年末出现的新型冠状病毒导致了全世界大流行，造成了超过1亿人口的感染和200万以上的死亡，对于人类社会造成了严重的威胁。我们团队前期研究发现抗病毒治疗对于新冠感染的治疗具有关键作用，而到目前为止，有效的新型冠状病毒抗病毒药物极其有限，而RNA病毒自身突变率较高的特性也影响了这些药物的前景，因此亟需一种能够快速应对现有新冠病毒变异以及新冠状病毒出现的抗病毒疗法。CRISPR/CasRX由于针对核酸本身，可以不受受体结合结构域（RBD）突变影响，从而具备这样的潜力，但其如何递送到易感细胞是一个关键瓶颈。本项目拟基于前期研究，建立以非复制型水泡性口炎病毒（VSV）为载体递送CRISPR/CasRX的抗病毒疗法，阐明其抗病毒作用和机制，填补国内外空白并协助疫情防控，并为抗其他囊膜RNA病毒研发提供理论依据。

The SARS-CoV-2 that appeared at the end of 2019 caused a pandemic around the world, causing infections of more than 100 million people and more than 2 million deaths, posing a serious threat to human society. Our team’s previous studies have found that antiviral is of great significance for the treatment of new coronavirus infections. So far, antiviral therapy for new coronaviruses is extremely limited, and the high mutation rate of the RNA virus has also affected the prospects of these drugs. Therefore, there is an urgent need for an antiviral therapy that can quickly respond to the mutation of the existing new coronavirus and the emergence of the new coronavirus. CRISPR/CasRX has such potential because it targets the nucleic acid itself and is not affected by RBD mutations, but how to deliver it to susceptible cells is a key bottleneck. This project intends to establish an antiviral therapy that uses non-replicating vesicular stomatitis virus (VSV) as a vector to deliver CRISPR/CasRX, clarify its antiviral effect and mechanism, assist in epidemic prevention and control. And provide a theoretical basis for the research and development against other enveloped RNA viruses.