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Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II.
Mol Ther 2005; 11(1):57-65MT

Abstract

Glycogen storage disease type II (GSD-II; Pompe disease) causes death in infancy from cardiorespiratory failure. The underlying deficiency of acid alpha-glucosidase (GAA; acid maltase) can be corrected by liver-targeted gene therapy in GSD-II, if secretion of GAA is accompanied by receptor-mediated uptake in cardiac and skeletal muscle. An adeno-associated virus (AAV) vector encoding human (h) GAA was pseudotyped as AAV8 (AAV2/8) and injected intravenously into immunodeficient GSD-II mice. High levels of hGAA were maintained in plasma for 24 weeks following AAV2/8 vector administration. A marked increase in vector copy number in the liver was demonstrated for the AAV2/8 vector compared to the analogous AAV2/2 vector. GAA deficiency in the heart and skeletal muscle was corrected with the AAV2/8 vector in male GSD-II mice, consistent with receptor-mediated uptake of hGAA. Male GSD-II mice demonstrated complete correction of glycogen storage in heart and diaphragm with the AAV2/8 vector, while female GSD-II mice had correction only in the heart. A biomarker for GSD-II was reduced in both sexes following AAV2/8 vector administration. Therefore, GAA production with an AAV2/8 vector in a depot organ, the liver, generated evidence for efficacious gene therapy in a mouse model for GSD-II.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15585406

Citation

Sun, Baodong, et al. "Efficacy of an Adeno-associated Virus 8-pseudotyped Vector in Glycogen Storage Disease Type II." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 11, no. 1, 2005, pp. 57-65.
Sun B, Zhang H, Franco LM, et al. Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II. Mol Ther. 2005;11(1):57-65.
Sun, B., Zhang, H., Franco, L. M., Young, S. P., Schneider, A., Bird, A., ... Koeberl, D. D. (2005). Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II. Molecular Therapy : the Journal of the American Society of Gene Therapy, 11(1), pp. 57-65.
Sun B, et al. Efficacy of an Adeno-associated Virus 8-pseudotyped Vector in Glycogen Storage Disease Type II. Mol Ther. 2005;11(1):57-65. PubMed PMID: 15585406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of an adeno-associated virus 8-pseudotyped vector in glycogen storage disease type II. AU - Sun,Baodong, AU - Zhang,Haoyue, AU - Franco,Luis M, AU - Young,Sarah P, AU - Schneider,Ayn, AU - Bird,Andrew, AU - Amalfitano,Andrea, AU - Chen,Y-T, AU - Koeberl,Dwight D, PY - 2004/06/14/received PY - 2004/10/01/revised PY - 2004/10/05/accepted PY - 2004/12/9/pubmed PY - 2005/5/5/medline PY - 2004/12/9/entrez SP - 57 EP - 65 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 11 IS - 1 N2 - Glycogen storage disease type II (GSD-II; Pompe disease) causes death in infancy from cardiorespiratory failure. The underlying deficiency of acid alpha-glucosidase (GAA; acid maltase) can be corrected by liver-targeted gene therapy in GSD-II, if secretion of GAA is accompanied by receptor-mediated uptake in cardiac and skeletal muscle. An adeno-associated virus (AAV) vector encoding human (h) GAA was pseudotyped as AAV8 (AAV2/8) and injected intravenously into immunodeficient GSD-II mice. High levels of hGAA were maintained in plasma for 24 weeks following AAV2/8 vector administration. A marked increase in vector copy number in the liver was demonstrated for the AAV2/8 vector compared to the analogous AAV2/2 vector. GAA deficiency in the heart and skeletal muscle was corrected with the AAV2/8 vector in male GSD-II mice, consistent with receptor-mediated uptake of hGAA. Male GSD-II mice demonstrated complete correction of glycogen storage in heart and diaphragm with the AAV2/8 vector, while female GSD-II mice had correction only in the heart. A biomarker for GSD-II was reduced in both sexes following AAV2/8 vector administration. Therefore, GAA production with an AAV2/8 vector in a depot organ, the liver, generated evidence for efficacious gene therapy in a mouse model for GSD-II. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/15585406/Efficacy_of_an_adeno_associated_virus_8_pseudotyped_vector_in_glycogen_storage_disease_type_II_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(04)01485-6 DB - PRIME DP - Unbound Medicine ER -