Stripped down vectors offer hope

Duchenne muscular dystrophy is a lethal condition caused by mutations in the dystrophin gene. Augmentation of the faulty copy by gene therapy represents a potential therapeutic answer, but delivery of functionally effective levels of the dystrophin gene in animal models has proved difficult. In the Early Edition of Proceedings of the National Academy of Sciences, Christiana DelloRusso and colleagues at Harvard Medical School, Boston, show that gutted adenoviral (Ad) vectors expressing full-length dystrophin can correct functional abnormalities of dystrophic muscle in mice (PNAS, DOI/10.1073 pnas.202300099, September 16, 2002).

So-called 'gutted' Ad vectors are modified such that all viral sequences are deleted, save those required for genome replication and packaging. DelloRusso et al. used vectors carrying either full-length human or mouse dystrophin cDNAs regulated by a powerful muscle-specific promoter. They observed that a single intramuscular injection restored dystrophin production to 25–30% of normal mouse limb muscle levels one month after treatment. ...