GENE-THERAPY FOR DUCHENNE MUSCULAR-DYSTROPHY - EARLY EXPERIENCES WITHLIPOSOME-MEDIATED GENE-TRANSFER

Duchenne muscular dystrophy is a lethal X-linked disorder in which mus cle degeneration results in confinement to a wheelchair by age 12 year s and death from respiratory failure by age 20 years. Gene therapy for this disorder poses unique challenges, related to the enormous size o f the gene, and to the difficulty of delivering a functional gene to t he millions of muscle fibers through-out the body. Adenoviral vectors are limited in their DNA capacity precluding their use to deliver an i ntact dystrophin gene cDNA, and the vectors themselves elicit an immun e response that will further limit their use. Cationic liposomes provi de a means to transfect cells bother viva and in vivo. In this study w e evaluated the use of a polycationic liposome formulation in deliveri ng are porter gene in cultured muscle cells and designed a new procedu re to enhance transfection efficiency of cationic liposomes, based on the precondensation of plasmid DNA with polylysine.