Viral vectors for gene transfer of micro-, mini-, or full-length dystrophin.
Gene therapy for Duchenne muscular dystrophy will require methods to deliver gene constructs encoding functional versions of dystrophin to the vast majority of a patient's musculature. Obstacles to achieving these goals include identifying which forms of dystrophin would be effective in a clinical setting and developing gene delivery shuttles capable of carrying and expressing dystrophin cassettes without toxic or adverse immunologic consequences. We review here recent work from our laboratory to identify sequences within dystrophin that are required to prevent development of dystrophic changes in muscle or which might be able to correct pre-existing damage. We also describe work aimed at developing viral shuttle vectors able to carry and express these dystrophin cassettes at high levels and in a muscle-specific fashion. While great challenges remain in developing methods for systemic gene delivery, we show that a variety of viral vectors are able to carry and express therapeutic levels of dystrophin when delivered directly to mouse skeletal muscle.
Department of Neurology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Jeannine M
JM
Scott
Sheng
S
Li
Scott Q
SQ
Harper
Robert
R
Welikson
Daniel
D
Bourque
Christiana
C
DelloRusso
Stephen D
SD
Hauschka
Jeffrey S
JS
Chamberlain
D000256:Adenoviridae; D000818:Animals; D000229:Dependovirus; D016189:Dystrophin / Q000235:genetics*; D018014:Gene Transfer Techniques / Q000639:trends; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000628:therapy; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics / Q000628:therapy*
D016189:Dystrophin