Adenine base editing repairs a muscular dystrophy-causing SGCA mutation in primary human muscle stem cells

Loss-of-function mutations in SGCA, encoding alpha-sarcoglycan, cause limb-girdle muscular dystrophy 2D/R3, an early onset, severe and rapidly progressive form of muscular dystrophy. We isolated human muscle stem cells from two donors with the common SGCA c.157G>A mutation affecting exon 2. Using adenine base editing, we corrected the mutation in the cells from both donors with >90% efficiency. We analyzed on-target editing as well as off-target editing at four predicted off-target loci using amplicon sequencing.