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PMID: 8943064 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 24 ·1996-11-26 ·Pages 14082-7

Kessler PD, Podsakoff GM, Chen X, McQuiston SA, Colosi PC, Matelis LA, Kurtzman GJ, Byrne BJ

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.

MeSH Terms
Animals Cell Line Dependovirus Erythropoiesis Erythropoietin/biosynthesis,genetics Escherichia coli Gene Expression Gene Transfer Techniques Genetic Therapy/methods Genetic Vectors Histocytochemistry Humans Injections, Intramuscular Lac Operon Mice Mice, Inbred BALB C Muscle, Skeletal/physiology Time Factors beta-Galactosidase/biosynthesis,genetics
Chemicals
Erythropoietin beta-Galactosidase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kessler P D
Peter Belfer Cardiac Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Podsakoff G M
Chen X
McQuiston S A
Colosi P C
Matelis L A
Kurtzman G J
Byrne B J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.24.14082
Published
1996-11-26
Pages
14082-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC19498
Subset
IM
Grants
NHLBI NIH HHS · HL51811 · United States
NHLBI NIH HHS · HL-27867 · United States
NHLBI NIH HHS · T32 HL007227 · United States
NHLBI NIH HHS · HL-07227 · United States
NHLBI NIH HHS · P01 HL051811 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.24.14082 PMC Full Text View journal details
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