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

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 <i>Bacteroides</i> 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.

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Publication Details

Journal
Science
Published
2025-11-13
DOI
https://doi.org/10.1126/science.adx7604
Citations
13
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
10.48

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article

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

Yiwei Sun, Yiming Huang, Harris H. Wang, Phuc Leo H. Vo et al.
13 citations
Science
CRISPR and Genetic Engineering
10.48
article

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

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

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 <i>Bacteroides</i> 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.

ScienceVol. 390(6774)
Howard Hughes Medical Institute (US), Columbia University (US)
National Science Foundation, Irma T. Hirschl Trust, National Institutes of Health, Irving Medical Center, Columbia University, Office of Naval Research, Air Force Research Laboratory
Openalex Percentile: Top 1%
CRISPR and Genetic Engineering
10.48
DOIOpen Access PDFOpenAlex
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