First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study

MMA is a devastating disease affecting individuals early in life, and no curative treatments are available. Due to the genetic basis of MMA, gene editing therapy represents an attractive alternative to liver transplantation. Conducting trials in MMA and similar rare diseases with fragile pediatric participants, especially with gene editing therapies, has numerous challenges [26,27,28].

We conducted the first-in-human trial of gene editing therapy in MMA, which enrolled young pediatric participants. Our study provides proof-of-concept that…