GENE DELIVERY TO SKELETAL-MUSCLE RESULTS IN SUSTAINED EXPRESSION AND SYSTEMIC DELIVERY OF A THERAPEUTIC PROTEIN

Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence t hat current methods of gene delivery can practically achieve this goal . In this study, we demonstrate that, following a single intramuscular administration of a recombinant adeno-associated virus (rAAV) vector containing the beta-galactosidase (AAV-lacZ) gene into adult BALB/c mi ce, protein expression was detected In myofibers for at least 32 weeks . A single intramuscular administration of an AAV vector containing a gene for human erythropoietin (AAV-Epo) into mice resulted in dose-dep endent secretion of erythropoietin and corresponding increases in red blood cell production that persisted for up to 40 weeks, primary human myotubes transduced in vitro with the AAV-Epo vector also showed dose -dependent production of Epo, These results demonstrate that rAAV vect ors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein f ollowing a single intramuscular administration, Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherit ed and acquired protein deficiencies.