Improved adenine base editors reduce unintended changes to nearby cytosines

The D108Q mutation in the adenosine deaminase TadA7.10 results in tenfold reduced cytosine deamination activity.

• Adenine base editors (ABEs) convert specific A-to-G sequences in DNA but also cause unwanted cytosine changes.
• The D108Q mutation reduces cytosine editing in ABE7.10, ABE8e, and ABE8s.
• The combination of D108Q with another mutation, V106W, lowers off-target effects on RNA.
• A different mutation, P48R, increases cytosine editing while significantly decreasing the rate of adenine editing.
• These findings enhance the capability of base editors for specific TC-to-TT or TC-to-TG conversions.

Simplified