Adenine base editors (ABEs) promise specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target DNA site and exhibit transcriptome-wide off-target RNA editing. To alleviate the ABE-mediated cytosine editing activity, here we engineered the commonly-used version of adenosine deaminase, TadA7.10, to contain rationally designed mutations. We ultimately found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited greatly reduced cytosine deamination activity, and conversely, ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity rather than adenine editing. We found that the D108Q mutation also reduces cytosine deamination activity in two recently-developed versions of ABE, ABE8e and ABE8s, and has a synergistic effect with V106W, a key mutation that reduces off-target RNA editing. On the other hand, by incorporating the P48R mutation into ABE7.10, we demonstrated TC-specific base editing tools that enable either TC-to-TT or TC-to-TG conversions, broadening the utility of base editors.

Genome Editing In article 2201825, Dong Hyun Jo, Sangsu Bae, Hyojin Lee and co‐workers develop a novel ribonucleoprotein (RNP) delivery platform, including Cas9 nuclease and base editor, via spongelike structured nanomaterials. This platform increases the delivery efficacy of RNPs in various cells and organs with different genes, and enhances the therapeutic efficiency for tumors, which enables a modular means of in vivo genome editing and other therapeutic purposes.