title: Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.
abstract: Somatic gene therapy has been proposed as a means to achieve systemic delivery of therapeutic proteins. However, there is limited evidence that 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 mice, 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-dependent 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 vectors are able to transduce skeletal muscle and are capable of achieving sustained expression and systemic delivery of a therapeutic protein following a single intramuscular administration. Gene therapy using AAV vectors may provide a practical strategy for the treatment of inherited and acquired protein deficiencies.
authors.affiliation: Peter Belfer Cardiac Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Kessler
authors.forename: G M
authors.initials: GM
authors.lastname: Podsakoff
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: S A
authors.initials: SA
authors.lastname: McQuiston
authors.forename: P C
authors.initials: PC
authors.lastname: Colosi
authors.forename: L A
authors.initials: LA
authors.lastname: Matelis
authors.forename: G J
authors.initials: GJ
authors.lastname: Kurtzman
authors.forename: B J
authors.initials: BJ
authors.lastname: Byrne
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus; D004920:Erythropoiesis; D004921:Erythropoietin / Q000096:biosynthesis* / Q000235:genetics; D004926:Escherichia coli; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006651:Histocytochemistry; D006801:Humans; D007273:Injections, Intramuscular; D007763:Lac Operon; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000502:physiology*; D013997:Time Factors; D001616:beta-Galactosidase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004921:Erythropoietin; D001616:beta-Galactosidase