MicroRNA-122-mediated liver detargeting enhances the tissue specificity of cardiac genome editing

We use base editing to eliminate the CaMKII-delta, a major driver of heart disease. We found that insertion of microRNA122 target sequence (miR122 TS) in the 3' UTR of the vector eliminates editing in the liver, in combination with heart-specific promoters to specifically edit in heart. Overall design: We delivered AAV-Tnnt2-SaCas9(-miR122) and AAV-Tnnt2-SPRY-ABE8e(-miR122) to mice. We harvested the murine hearts and livers to investigate the gene edit effect.