Engineering of efficient photoactivatable A to I RNA base editor for gene therapy in vivo

Here, we developed a photoactivatable RNA adenosine base editor by harnessing a compact Cas13 variant and a split ADAR2 deaminase fused with the Magnets system, which is activated through blue light-induced dimerization. PA rABE achieves highly efficient editing on endogenous mRNA with minimal bystander editing and off-target effects. By editing a phosphorylation site of the endogenous CTNNB1 gene, PA rABE stabilized beta catenin protein and significantly activated Wnt signaling in vivo.