EXPRESSION OF A RECOMBINANT DYSTROPHIN IN MDX MICE USING ADENOVIRUS VECTOR

Genetic deficiencies may be compensated by delivery of the appropriate gene to the affected tissue(s) by somatic gene transfer. In this stud y, recombinant adenoviruses (defective for replication) carrying a cDN A coding for a truncated dystrophin or 'minidystrophin' (Ad.dys), asso ciated to adenoviruses carrying a beta-galactosidase reporter gene (Ad .beta gal), were administered locally to evaluate the biochemical corr ection of the genetic defect in mdx mice mutants. Both genes were plac ed under the control of muscle specific regulatory elements. Two weeks after a single intramuscular injection of Ad.dys, injected muscles sh owed a significant increase in the percentage of dystrophin positive f ibres when compared to muscles either untreated or injected with Ad.be ta gal only. Intramuscular injection of the adenoviral expression vect ors elicited a local deleterious effect on muscle morphology, rarefact ion of myofibres at the site of injection, calcifications and fibrosis were much more marked in comparison to control muscles injected with vehicle. beta-galactosidase was exclusively expressed within myofibres in a segmental fashion. Regional co-localization of beta-galactosidas e and dystrophin expression gives further support to the demonstration of adenoviral induced expression of the recombinant genes.