美国哈佛大学George M. Church等研究人员合作发现，一个互换的遗传密码可以防止病毒感染和基因转移。相关论文于2023年3月15日在线发表在《自然》杂志上。

研究人员表明，尽管在全基因组范围内删除了64个密码子中的3个以及以前必不可少的同源tRNA和释放因子基因，但这种移动转运RNA（tRNA）仍能使基因转移并允许病毒在大肠杆菌中复制。然后，研究人员通过发现病毒的tRNA提供特别有效的密码子重新分配来建立基因防火墙，使其能够开发出带有氨基酸互换的遗传密码的细胞，在翻译过程中将六个丝氨酸密码子中的两个重新分配为亮氨酸。这种氨基酸交换的遗传密码使细胞通过错误翻译病毒蛋白质组而对病毒感染产生抵抗力，并通过工程化地依赖丝氨酸密码子来生产需要白氨酸的蛋白质而防止合成遗传信息的逃逸。由于这些细胞可能因抗病毒而比野生生物具有选择优势，研究人员还重新利用第三个密码子，通过依赖自然界中没有的氨基酸，对这种抗病毒宿主进行生物控制。这些结果可能为旨在使任何生物体安全地抵抗所有天然病毒并防止遗传信息流入和流出转基因生物体的一般策略提供基础。

据介绍，有人提出对生物体的遗传密码进行改造，通过防止病毒感染和基因转移，为自然生态系统提供一道防火墙。然而，许多病毒和移动遗传元件编码了翻译装置的一部分，有可能使基于遗传密码的防火墙失去效力。

附：英文原文

Title: A swapped genetic code prevents viral infections and gene transfer

Author: Nyerges, Akos, Vinke, Svenja, Flynn, Regan, Owen, Sin V., Rand, Eleanor A., Budnik, Bogdan, Keen, Eric, Narasimhan, Kamesh, Marchand, Jorge A., Baas-Thomas, Maximilien, Liu, Min, Chen, Kangming, Chiappino-Pepe, Anush, Hu, Fangxiang, Baym, Michael, Church, George M.

Issue&Volume: 2023-03-15

Abstract: Engineering the genetic code of an organism has been proposed to provide a firewall from natural ecosystems by preventing viral infections and gene transfer1,2,3,4,5,6. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus7,8,9, potentially rendering a genetic-code-based firewall ineffective. Here we show that such mobile transfer RNAs (tRNAs) enable gene transfer and allow viral replication in Escherichia coli despite the genome-wide removal of 3 of the 64 codons and the previously essential cognate tRNA and release factor genes. We then establish a genetic firewall by discovering viral tRNAs that provide exceptionally efficient codon reassignment allowing us to develop cells bearing an amino acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino acid-swapped genetic code renders cells resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. As these cells may have a selective advantage over wild organisms due to virus resistance, we also repurpose a third codon to biocontain this virus-resistant host through dependence on an amino acid not found in nature10. Our results may provide the basis for a general strategy to make any organism safely resistant to all natural viruses and prevent genetic information flow into and out of genetically modified organisms.

DOI: 10.1038/s41586-023-05824-z

Source: https://www.nature.com/articles/s41586-023-05824-z