开发CRISPR作为抗病毒策略来对抗SARS-CoV-2和流感
Timothy R Abbott1, Girija Dhamdhere2, Yanxia Liu1
1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Cell
|May 1, 2020
概括
一个新的CRISPR-Cas13系统,PAC-MAN,有效地降解了人体细胞中的SARS-CoV-2和流感RNA. 这种预防性抗病毒策略对广泛的冠状病毒抑制具有前景.
科学领域:
- 分子生物学
- 病毒学
- 基因编辑技术
背景情况:
- COVID-19 疫情凸显了对新兴病毒的新型抗病毒疗法的迫切需要.
- 目前的疫苗和药品不足以应对像SARS-CoV-2这样快速发展的病毒威胁.
- 针对RNA的抗病毒策略为广泛的病毒抑制提供了有希望的途径.
研究的目的:
- 开发和评估一种基于CRISPR-Cas13的病毒RNA降解系统.
- 评估该系统对人类细胞中的SARS-CoV-2和流感A病毒 (IAV) 的有效性.
- 探索其作为全冠状病毒抑制策略的潜力.
主要方法:
- 设计和选的CRISPRRNAs (crRNAs) 针对病毒RNA的保存区域.
- 使用CRISPR-Cas13系统,称为PAC-MAN (人类细胞中的预防性抗病毒CRISPR),用于向RNA降解.
- 在感染SARS-CoV-2和活 H1N1 IAV的人类肺上皮细胞中测试了PAC-MAN的有效性.
主要成果:
- PAC-MAN 在人类肺上皮细胞中有效降解了 SARS-CoV-2 序列和活 H1N1 IAV 的 RNA.
- 已确定专门针对SARS-CoV-2的功能crRNA.
- 生物信息分析表明,六种crRNA可以向已知冠状病毒的90%以上.
结论:
- 通过降解病毒RNA,PAC-MAN系统对SARS-CoV-2和IAV表现出强大的抗病毒活性.
- PAC-MAN代表了一种针对广泛的冠状病毒的预防和治疗干预的可行策略.
- 进一步开发安全有效的呼吸道输送可以使PAC-MAN成为关键的泛冠状病毒抑制工具.
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