Adenine base editor engineering reduces editing of bystander cytosines

Jul 2, 2021Nature biotechnology

Improved adenine base editors reduce unintended changes to nearby cytosines

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Abstract

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.

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