美国加州大学旧金山分校Seth L. Shipman团队报道反转录子用于DNA生成和基因组编辑的实验调查。2024年9月17日，国际知名学术期刊《自然—生物技术》在线发表了这一成果。

研究人员表示，反转录子是细菌免疫系统，利用反转录的DNA（RT-DNA）检测噬菌体感染。它们也被用于基因组编辑，通过修改使得RT-DNA编码编辑供体。反转录子在细菌基因组中常见，已经通过生物信息学预测了数千种独特的反转录子。然而，只有少数通过实验表征。

研究人员增加了实验研究的反转录子数量，发现了62种无法仅从反转录子序列中预测的自然RT-DNA。研究人员合成了100多种以前未经测试的反转录子，鉴定它们产生的自然RT-DNA序列，量化它们的RT-DNA产量，并测试使用反转录子衍生供体编辑细菌、噬菌体和人类基因组的相对效率。

研究人员观察到不同反转录子的RT-DNA产量和编辑率存在巨大差异，发现性能最佳的编辑器来自反转录子系统谱的一个子集，并且在先前研究中使用的编辑器中表现优异，在人类细胞中达到高达40%的精确编辑率。

附：英文原文

Title: An experimental census of retrons for DNA production and genome editing

Author: Khan, Asim G., Rojas-Montero, Matas, Gonzlez-Delgado, Alejandro, Lopez, Santiago C., Fang, Rebecca F., Crawford, Kate D., Shipman, Seth L.

Issue&Volume: 2024-09-17

Abstract: Retrons are bacterial immune systems that use reverse-transcribed DNA (RT-DNA) to detect phage infection. They are also deployed for genome editing, where they are modified so that the RT-DNA encodes an editing donor. Retrons are common in bacterial genomes, and thousands of unique retrons have been predicted bioinformatically. However, few have been characterized experimentally. We add to the corpus of experimentally studied retrons, finding 62 empirically determined, natural RT-DNAs that are not predictable from the retron sequence alone. We synthesize >100 previously untested retrons to identify the natural sequence of RT-DNA they produce, quantify their RT-DNA production and test the relative efficacy of editing using retron-derived donors to edit bacterial, phage and human genomes. We observe large diversity in RT-DNA production and editing rates across retrons, finding that top-performing editors are drawn from a subset of the retron phylogeny and outperform those used in previous studies, reaching precise editing rates of up to 40% in human cells.

DOI: 10.1038/s41587-024-02384-z

Source: https://www.nature.com/articles/s41587-024-02384-z