Intraarterial delivery of naked plasmid DNA expressing full-length mouse dystrophin in the mdx mouse model of duchenne muscular dystrophy.
Our previous studies have demonstrated that the intraarterial delivery of naked plasmid DNA leads to high levels of foreign gene expression throughout the muscles of the targeted limb. Although the procedure was first developed in rats and then extended to nonhuman primates, the present study has successfully implemented the procedure in normal mice and the mdx mouse model for Duchenne muscular dystrophy. After intraarterial delivery of plasmid DNA expressing the normal, full-length mouse dystrophin from either the cytomegalovirus promoter or a muscle-specific human desmin gene control region, mdx mouse muscle stably expressed dystrophin in 1-5% of the myofibers of the injected hind limb for at least 6 months. This expression generated an antibody response but no apparent cellular response.
Departments of Pediatrics and Medical Genetics, Waisman Center, University of Wisconsin-Madison, Madison, WI 53705, USA.
Goufeng
G
Zhang
James J
JJ
Ludtke
Christine
C
Thioudellet
Patricia
P
Kleinpeter
Michael
M
Antoniou
Hans
H
Herweijer
Serge
S
Braun
Jon A
JA
Wolff
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004247:DNA / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000628:therapy*; D010957:Plasmids / Q000235:genetics
D016189:Dystrophin; D004247:DNA; D003402:Creatine Kinase