ABSTRACT
Muscular dystrophy is a systemic disease. Methods outlined in this chapter have shown great potential in restoring near-normal histology to muscle fibers and in improving the function of whole muscles in in vivo assays following the use of virus-based vectors for gene delivery.Most of these studies focus on local delivery, assaying the efficacy of the vectors at the level of individual muscles in small animal models. A limitation of these model becomes evident when attempts are made to deliver these vectors regionally or systemically. This process is further compounded when studies are extended into large animal models. In the clinical setting, treatment that can safely confer significant benefit, both as perceived by the patient and as measured through standardized strength testing, must be the ultimate goal. This translation from local to systemic delivery, from ‘‘benchtop to bedside,’’ may be one of the greatest challenges faced in gene therapy for muscular dystrophy. The complete reversal of histopathological signs of muscular dystrophy in several murine models following germline gene transfer has prompted consideration of a wide range of strategies for achieving systemic gene transfer. In this chapter, we focus specifically on strategies pertaining to the use of virus-based vectors to directly transduce striated muscle in situ, thereby complementing advances in vector development described in other chapters.
