An adenine base editor variant expands context compatibility

ABE8r outperforms existing adenine base editors in correcting disease-associated G:C-to-A:T transitions in the human genome.

• ABE8r combines an evolved adenosine deaminase variant, TadA8r, with a Cas9 nickase, enhancing gene-editing capabilities.
• TadA8r demonstrates improved deoxyadenosine deamination speed, particularly on GA pairs, compared to earlier TadA variants.
• The editing window is expanded at the protospacer adjacent motif-distal end, allowing for more effective editing of target sites.
• ABE8r shows a controlled off-target profile while effectively editing clinically relevant sites that are challenging for existing editors.
• Specific applications include editing of the PCSK9 site, which may lower low-density lipoprotein cholesterol, and the ABCA4 mutation linked to Stargardt disease.

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