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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.

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  • Publisher Full Text

    • Authors+Show Affiliations

    Sun B
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
    Zhang H
    No affiliation info available
    Franco LM
    No affiliation info available
    Young SP
    No affiliation info available
    Schneider A
    No affiliation info available
    Bird A
    No affiliation info available
    Amalfitano A
    No affiliation info available
    Chen YT
    No affiliation info available
    Koeberl DD
    No affiliation info available

    MeSH

    AnimalsCell LineDependovirusFemaleGene Expression RegulationGenetic TherapyGenetic VectorsGlucan 1,4-alpha-GlucosidaseGlucoseGlycogen Storage Disease Type IIHumansMaleMiceMice, KnockoutMotor ActivitySex Characteristicsalpha-Glucosidases

    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 -