近日，教授Harris H. Wang及其研究小组提出了利用CRISPR相关转座酶对体内共生细菌进行宏基因组编辑。2025年11月13日出版的《科学》发表了这项成果。

课题组研究人员介绍了宏基因组编辑（metagenomics Editing, MetaEdit）作为微生物组工程的平台技术，该技术通过广泛结合的载体来优化CRISPR相关转座酶，以单核苷酸基因组分辨率的新途径直接修饰来自小鼠和人类的多种天然共生细菌。使用MetaEdit，研究团队通过整合代谢有效载荷实现了原生小鼠拟杆菌的体内遗传捕获，使哺乳动物肠道中的可调节生长控制与膳食菊粉相结合。课题组进一步展示了片段丝状细菌的体内编辑，这是一种免疫调节的小肠微生物物种，难以培养。总的来说，这项工作提供了一个范例，可以精确地操纵原生群落中千兆位元基因组库中的单个细菌。

据介绍，尽管宏基因组测序揭示了哺乳动物肠道中丰富的微生物多样性，但对微生物组中特定物种进行遗传改变的方法非常有限。

附：英文原文

Title: Metagenomic editing of commensal bacteria in vivo using CRISPR-associated transposases

Author: Diego Rivera Gelsinger, Carlotta Ronda, Junjie Ma, Om B. Kar, Madeline Edwards, Yiming Huang, Chrystal F. Mavros, Yiwei Sun, Tyler Perdue, Phuc Leo Vo, Ivaylo I. Ivanov, Samuel H. Sternberg, Harris H. Wang

Issue&Volume: 2025-11-13

Abstract: Although metagenomic sequencing has revealed a rich microbial biodiversity in the mammalian gut, methods to genetically alter specific species in the microbiome are highly limited. Here, we introduce Metagenomic Editing (MetaEdit) as a platform technology for microbiome engineering that uses optimized CRISPR-associated transposases delivered by a broadly conjugative vector to directly modify diverse native commensal bacteria from mice and humans with new pathways at single-nucleotide genomic resolution. Using MetaEdit, we achieved in vivo genetic capture of native murine Bacteroides by integrating a metabolic payload that enables tunable growth control in the mammalian gut with dietary inulin. We further show in vivo editing of segmented filamentous bacteria, an immunomodulatory small-intestinal microbial species recalcitrant to cultivation. Collectively, this work provides a paradigm to precisely manipulate individual bacteria in native communities across gigabases of their metagenomic repertoire..

DOI: adx7604

Source: https://www.science.org/doi/10.1126/science.adx7604