Gene therapy for Duchenne muscular dystrophy - Early experiences with liposome-mediated gene transfer

Duchenne muscular dystrophy is a lethal X-linked disorder in which muscle degeneration results in confinement to a wheelchair by age 12 years and death from respiratory failure by age 20 years. Gene therapy for this disorder poses unique challenges, related to the enormous size of the gene, and to the difficulty of delivering a functional gene to the millions of muscle fibers through-out the body. Adenoviral vectors are limited in their DNA capacity precluding their use to deliver an intact dystrophin gene cDNA, and the vectors themselves elicit an immune response that will further limit their use. Cationic liposomes provide a means to transfect cells bother viva and in vivo. In this study we evaluated the use of a polycationic liposome formulation in delivering areporter gene in cultured muscle cells and designed a new procedure to enhance transfection efficiency of cationic liposomes, based on the precondensation of plasmid DNA with polylysine