Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations

Journal: Nature Cell Biology

Published: 2021-05-10

DOI: 10.1038/s41556-021-00671-4

Affiliations: 11

Authors: 21

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Research Highlight

A safer base editor

© traffic_analyzer/DigitalVision Vectors/Getty Images

© traffic_analyzer/DigitalVision Vectors/Getty Images

A new gene-editing tool allows researchers to rewrite individual letters of DNA, or genetic bases, with lower risk of off-target activity.

CRISPR–Cas9 technology is an incredibly powerful way to edit genes, but it sometimes causes unintended edits in off-target regions.

Devised by researchers at ShanghaiTech University, the new gene-editing method could allow for safe and effective correction of disease-causing mutations or the precise manipulation of genes for therapeutic gain.

The system uses a base-editing enzyme tethered to a counteracting ‘antidote’ protein. When the tool binds at target sites, the antidote is cleaved off and the base editor alters the desired DNA — swapping one base for another — without introducing unintended mutations.

The researchers used their base-editing method in mice to create shortened versions of PCSK9, a protein involved in cholesterol metabolism. The mice subsequently had lower levels of cholesterol in their blood, with no detectable off-target mutations in either their DNA or RNA.

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  1. Nature Cell Biology 23, 552–563 (2021). doi: 10.1038/s41556-021-00671-4
Institutions Share
Zhongnan Hospital, WHU, China 0.38
ShanghaiTech University, China 0.28
University of Chinese Academy of Sciences (UCAS), China 0.13
Shanghai Institute of Nutrition and Health (SINH), CAS, China 0.09
CAS Center for Excellence in Molecular Cell Science, SIBS CAS, China 0.06
Institute of Biochemistry and Cell Biology (IBCB), SIBS CAS, China 0.06