I used two adenine base editors—ABE8e-SpRY and ABE8e-NG—to target a heterozygous mutation site where the wild-type allele is G and the mutant allele is A. The goal was to convert the A (mutant) back to G using ABE, which catalyzes A•T to G•C conversions.

After editing and Sanger sequencing, I unexpectedly observed an increase in the proportion of A at the target site in both patient-derived samples and across both editors by 20% compared to the control.

I'm trying to determine whether this could be an artifact of sequencing, or if there are other explanations that could account for this outcome.

Has anyone observed similar phenomena with ABE editing? Any insights into how to interpret such a result would be greatly appreciated.