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Extended tropism of an adenoviral vector does not circumvent the maturation‐dependent transducibility of mouse skeletal muscle
Author(s) -
van Deutekom Judith C. T.,
Cao Baohong,
Pruchnic Ryan,
Wickham Thomas J.,
Kovesdi Imre,
Huard Johnny
Publication year - 1999
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/(sici)1521-2254(199911/12)1:6<393::aid-jgm65>3.0.co;2-u
Subject(s) - tropism , transduction (biophysics) , viral vector , biology , extracellular matrix , skeletal muscle , tissue tropism , microbiology and biotechnology , gene delivery , myocyte , adenoviridae , genetic enhancement , virology , gene , endocrinology , recombinant dna , biochemistry , virus
Background Efficient adenoviral gene delivery to mature skeletal muscle has been hindered by different factors. The low levels of adenoviral attachment receptor (CAR) that have been reported in this tissue may be a limiting factor. Therefore, adenoviral transduction of mature muscle may be improved by extending the tropism of the adenoviral vectors to attachment receptors that are highly expressed in mature myofibers. In this study, we have investigated whether an extended tropism adenoviral vector which additionally attaches to the broadly expressed heparan‐containing receptors (AdPK) can bypass the maturation‐dependent adenoviral transducibility of mouse skeletal muscle. Methods The adenoviral vector AdPK carrying the LacZ gene was evaluated as a gene delivery vehicle in mouse skeletal muscle at different maturities in vitro and in vivo . The viral transduction efficiencies were determined by histochemical and ONPG analysis of the β‐galactosidase activity level. Results Higher transduction efficiencies were detected in immature muscle from normal mice, and in mature muscle from merosin‐deficient dy/dy mice (carrying myofibers with an impaired extracellular matrix) and dystrophin‐deficient mdx mice (showing a high level of myoblast activity) when compared to mature muscle from normal mice. Conclusions Despite the enhanced attachment characteristics, the extended tropism adenoviral vector is, similarly to the wild‐type adenoviral vector in previous studies, still hindered by both a protective extracellular matrix and the diminished myoblast‐mediation in mature muscle. Copyright © 1999 John Wiley & Sons, Ltd.