Genome biologyOct 22, 2025

Precise DNA base editing with low unwanted changes in mammal embryos using glycosylase enzymes

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

AYBE and gGBE edited mammalian embryos efficiently with rare DNA off-target signals, though AYBE-derived TadA8e-V106W showed low-frequency RNA off-target editing.

Evidence

Platform experiments used GOTI in mouse embryos, transcriptome-wide RNA analysis, and editing tests in mouse and sheep embryos plus newborn lambs.

Caveat

The abstract reports embryo and livestock editing performance, not clinical safety or long-term outcomes after editing.

Simplified

Developing glycosylase-based base editors () to broaden the editing scope is highly desirable for biomedical research and agricultural applications. However, the off-target effects and applicability of gBEs need further investigation. We employ GOTI to detect rare DNA off-target events in mouse embryos injected with N-methylpurine glycosylase-based AYBE and gGBE. Transcriptome-wide RNA analysis reveals that TadA8e-V106W, derived from AYBE, induces low-frequency RNA off-target editing. Both base editors efficiently induce A/G-to-Y editing in mouse and sheep embryos, and in newborn lambs. The robust efficiency and specificity of AYBE and gGBE underscore their potential for clinical applications and genetic improvement in livestock.

Key numbers

47.37% to 99.90%

A-to-other Editing Efficiency

Editing efficiencies for AYBE-V106W across various target sites.

21.00% to 85.29%

G-to-other Editing Efficiency

Editing efficiencies for gGBE in sheep embryos.

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Funding

Competing interests

0%of authors

0 of 16

authors report competing interests

16 report none

PubMed

Precise DNA base editing with low unwanted changes in mammal embryos using glycosylase enzymes

Abstract

Key numbers

Full Text

Funding

Competing interests

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