Gene Therapy for Duchenne Muscular Dystrophy

CRISPR-Cas9 Mediated Gene Editing in DMD Patient-Derived iPSC

Abstract

Duchenne Muscular Dystrophy (DMD) is a severe muscle degener- ation disease caused by gene mutations in the dystrophin gene. The CRISPR-Cas9 system is an emerging potential gene editing tool that utilizes the Cas9 nuclease and DNA double strand breaks (DSB) to make site- specific gene corrections. Induced human pluripotent stem cells (iPSC) are derived from the human body and reprogrammed to become potential stem cells that can differentiate into various human cell lineages. Using CRISPR-Cas9 in iPSCs to correct certain exon mutations in the dystrophin gene provides great advantages in both efficacy and low immunogenicity. This article reviews four main CRISPR-mediated exon correction methods that correct various mutations occurring across the dystrophin gene. In addition, this review discusses current developments and studies utilizing CRISPR-Cas9 to perform gene editing in iPSC derived from DMD patients and evaluates the feasibility of such an integrated gene therapy. To the end, this review compares the advantages and limitations of this gene therapy to other traditional methods and provides future prospective regarding further implementation.