Electroporation of Corrective Nucleic Acids (CNA) In Vivo to Promote Gene Correction in Dystrophic Muscle

Non-viral gene transfer into skeletal muscle in vivo is enhanced by electroporation (EP) to efficiencies far beyond any other (non-EP) method reported to date. Electroporation consistently delivers high levels of transgene to muscle and has been used extensively for the delivery of therapeutic transgenes to dystrophic mouse muscle such as the mdx mouse model of human Duchenne muscular dystrophy (DMD). Since the earliest applications, electroporation has consistently and reproducibly achieved highly efficient DNA delivery to a high proportion (greater than 70%) of fibres in treated muscles. This manuscript describes a methodology for introduction of corrective nucleic acids (CNAs) for the purpose of correcting the dystrophin gene (DMD ^mdx ) mutation responsible for muscular dystrophy in the mdx mouse model of human DMD by targeted corrective gene conversion (TCGC).