Multiplex base editing to convert TAG into TAA codons in the human genome

Yuting Chen, Eriona Hysolli (), Anlu Chen, Stephen Casper, Songlei Liu, Kevin Yang, Chenli Liu () and George Church ()
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Yuting Chen: Harvard Medical School
Eriona Hysolli: Harvard Medical School
Anlu Chen: Harvard Medical School
Stephen Casper: Harvard Medical School
Songlei Liu: Harvard Medical School
Kevin Yang: Harvard Medical School
Chenli Liu: Chinese Academy of Sciences
George Church: Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Whole-genome recoding has been shown to enable nonstandard amino acids, biocontainment and viral resistance in bacteria. Here we take the first steps to extend this to human cells demonstrating exceptional base editing to convert TAG to TAA for 33 essential genes via a single transfection, and examine base-editing genome-wide (observing ~40 C-to-T off-target events in essential gene exons). We also introduce GRIT, a computational tool for recoding. This demonstrates the feasibility of recoding, and highly multiplex editing in mammalian cells.

Date: 2022
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DOI: 10.1038/s41467-022-31927-8

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