Molecular therapy. Nucleic acidsSep 8, 2025

A set of precise and adjustable DNA base editors using split TadA-8e enzyme

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Split TadA-8e editors may make adenine base editing more controllable while reducing DNA and RNA off-target effects.

Evidence

A base-editor engineering study split TadA-8e in ABE8e for rapamycin-induced FRB-FKBP12 dimerization and extended the split site to AYBE and eA&C-BEmax, with similar or slightly lower on-target editing and fewer off-targets than the parent editors.

Caveat

The abstract reports tool performance rather than clinical use, so safety and therapeutic value remain inferred from editing assays rather than disease-treatment outcomes.

Simplified

Adenine base editors (ABEs) enable efficient A-to-G base conversions in genomic DNA, serving as powerful tools for basic research and clinical disease treatment. TadA-8e with high processive and compatibility makes ABE8e to be the most widely used adenine base editor and has also facilitated the creation of more elegant base editors based on TadA-8e fusion, such as AYBE and eA&C-BEmax. However, ABE8e has more off-target events including DNA off-target and RNA off-target, which raises safety concerns for precision gene editing. Here, we split the TadA-8e of ABE8e (sABE8e) to enable controlled adenine base editing through rapamycin-induced dimerization between FRB and FKBP12. sABE8e has comparable on-target adenine editing activity to ABE8e while maintaining reduced DNA and RNA off-target effects. Harnessing this site of split TadA-8e, we have also developed controllable AYBE (sAYBE) and eA&C-BEmax (seA&C-BEmax), which both offer similar or slightly low base editing efficiency with decreased off-targets compared to AYBE or eA&C-BEmax. These precise and controllable base editing tools will advance the future application of base editors in basic research and clinical disease treatment.

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Funding

Competing interests

No relevant relationships were reported.

PubMed

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A set of precise and adjustable DNA base editors using split TadA-8e enzyme

Abstract

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Abstract

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