High-efficiency plasmid gene transfer into dystrophic muscle

• Published in: Gene therapy Vol. 10; no. 6; pp. 504 - 512
• Main Authors: GOLLINS, H, MCMAHON, J, WELLS, K. E, WELLS, D. J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 02.03.2003
• Subjects: Animals; beta-Galactosidase - genetics; Biological and medical sciences; Connective tissue; Connective tissues; Deoxyribonucleic acid; DNA; Duchenne's muscular dystrophy; Dystrophin - genetics; Dystrophin - metabolism; Efficiency; Electroporation - methods; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene transfer; Genetic Therapy - methods; Injection; Injections, Intramuscular; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred mdx; Molecular and cellular biology; Muscle, Skeletal - metabolism; Muscular Dystrophies - therapy; Phenotypes; Plasmids - administration & dosage; Skeletal muscle; Transfection; United Kingdom; hyaluronidase; muscular dystrophy; fibres; plasmid; Genetics; gene therapy; electroporation; skeletal muscle
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301927

The efficiency of plasmid gene transfer in skeletal muscle is significantly enhanced by pretreatment with hyaluronidase and the application of an electrical field to the muscle following the injection of plasmid DNA, a process referred to as electrotransfer. However, the presence of increased levels of connective tissue in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), may affect the efficiency of this process. Here we demonstrate that the efficiency of electrotransfer is not affected by increased levels of connective tissue in the mdx mouse model of DMD and that any damage induced by the electrotransfer process is not exacerbated in the dystrophic phenotype. However, increasing the concentration of hyaluronidase does not improve transfection efficiencies further. Unlike direct injection of plasmid DNA, the efficiency of electrotransfer is not dependent upon the sex and age of mice used. The combined treatment of hyaluronidase and electrotransfer results in highly efficient gene transfer in dystrophic muscle with limited muscle damage.