Duchenne muscular dystrophy (DMD) is a monogenic disorder and a candidate for therapeutic genome editing. There have been several recent reports of genome editing in preclinical models of DMD, however, the long-term persistence and safety of these genome editing approaches have not been addressed.
Here, researchers show that genome editing and dystrophin protein restoration is sustained in the mdx mouse model of DMD for 1 year after a single intravenous administration of an adeno-associated virus that encodes CRISPR (AAV-CRISPR). They also show that AAV-CRISPR is immunogenic when administered to adult mice; however, humoral and cellular immune responses can be avoided by treating neonatal mice. Additionally, they describe unintended genome and transcript alterations induced by AAV-CRISPR that should be considered for the development of AAV-CRISPR as a therapeutic approach.
This study shows the potential of AAV-CRISPR for permanent genome corrections and highlights aspects of host response and alternative genome editing outcomes that require further study.
