Downregulation of CD46 during muscle differentiation: implications for gene transfer to human skeletal muscle using group B adenoviruses.
Adenoviral vectors that use the coxsackievirus and adenovirus receptor do not transduce mature muscle efficiently. Group B adenoviruses use CD46 as their cell attachment receptor. To evaluate the utility of vectors based on group B adenoviruses for gene transfer to human skeletal muscle, we assessed the expression of CD46 in biopsied normal skeletal muscle samples and in muscles from patients with Duchenne muscular dystrophy. Transcript levels of CD46 were extremely low in mature muscle and CD46 immunoreactivity was detected only on blood vessels in the muscle sections. Although myoblasts cultured from biopsied samples had robust cell surface CD46 expression by flow cytometry, CD46 transcript levels were barely detectable after differentiation of the myoblasts into myotubes. The myotubes were also much less susceptible to infection with an adenoviral vector carrying the fiber of serotype 35 adenovirus (AdF35). These results suggest that for skeletal muscle, vectors derived from group B adenoviruses may not be a suitable alternative to the commonly used Ad5 vectors.
Larochelle
Nancy
N
Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
Deol
Jatinderpal R
JR
Srivastava
Vinit
V
Allen
Carol
C
Mizuguchi
Hiroyuki
H
Karpati
George
G
Holland
Paul C
PC
Nalbantoglu
Josephine
J
D000256:Adenoviridae / Q000378:metabolism*; D001706:Biopsy; D002454:Cell Differentiation; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics*; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne; D032446:Myoblasts; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods*; D001616:beta-Galactosidase
D051916:Membrane Cofactor Protein; D001616:beta-Galactosidase