Plasmid DNA is superior to viral vectors for direct gene transfer into adult mouse skeletal muscle.
Direct gene transfer into skeletal muscle offers several therapeutic possibilities. We assessed direct intramuscular injection of recombinant plasmids, adenovirus, or retrovirus in normal or regenerating muscles of mice. The incorporation and expression of reporter genes introduced by any of these three vectors is greater in regenerating than in mature muscle. In regenerating muscle, pure DNA and adenovirus result in equivalent numbers of fibers expressing reporter gene (> 10%), but adenovirus also induces considerable cellular infiltration. In mature muscle, recombinant DNA is better than adenovirus. Retrovirus failed to infect mature muscle fibers and was less effective than plasmid DNA or adenovirus in regenerating muscle. The surprisingly high relative efficiency of pure plasmid DNA suggests that this method will provide a simple, safe and viable alternative for gene therapy involving muscle tissue.
Davis
H L
HL
Physiotherapy Program, Faculty of Health Science, University of Ottawa, Canada.
Demeneix
B A
BA
Quantin
B
B
Coulombe
J
J
Whalen
R G
RG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology; D004274:DNA, Recombinant; D004279:DNA, Viral; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010957:Plasmids; D012038:Regeneration / Q000187:drug effects; D012190:Retroviridae / Q000235:genetics
D004179:Cobra Cardiotoxin Proteins; D004274:DNA, Recombinant; D004279:DNA, Viral