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Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.
Mol Ther. 2006 Jan; 13(1):127-34.MT

Abstract

Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via nonviral regulatory elements (PEPCK promoter/ApoE enhancer) would facilitate long-term efficacy and decrease propensity to generate anti-hGAA antibody responses against hepatically secreted hGAA. Intravenous delivery of FDAdhGAA into GAA-tolerant or nontolerant GAA-KO mice resulted in long-term hepatic secretion of hGAA. Specifically, nontolerant mice achieved complete reversal of cardiac glycogen storage and near-complete skeletal glycogen correction for at least 180 days and tolerant mice for minimally 300 days coupled with the preservation of muscle strength. Anti-hGAA antibody levels in both mouse strains were significantly less relative to those previously generated by CMV-driven hGAA expression in nontolerant GAA-KO mice. However, plasma GAA levels decreased in nontolerant GAA-KO mice despite long-term intrahepatic GAA expression from the persistent vector. This intriguing result is discussed in light of other examples of "tolerance" induction by gene-transfer-based approaches.

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  • Publisher Full Text

    • Authors+Show Affiliations

    Kiang A
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
    Hartman ZC
    No affiliation info available
    Liao S
    No affiliation info available
    Xu F
    No affiliation info available
    Serra D
    No affiliation info available
    Palmer DJ
    No affiliation info available
    Ng P
    No affiliation info available
    Amalfitano A
    No affiliation info available

    MeSH

    AdenoviridaeAnimalsEnhancer Elements, GeneticGene Transfer TechniquesGenetic VectorsGlycogenGlycogen Storage Disease Type IIHumansImmune ToleranceLiverMiceMice, KnockoutMuscle, SkeletalMyocardiumPromoter Regions, Geneticalpha-Glucosidases

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16169280

    Citation

    Kiang, Anne, et al. "Fully Deleted Adenovirus Persistently Expressing GAA Accomplishes Long-term Skeletal Muscle Glycogen Correction in Tolerant and Nontolerant GSD-II Mice." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 13, no. 1, 2006, pp. 127-34.
    Kiang A, Hartman ZC, Liao S, et al. Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Mol Ther. 2006;13(1):127-34.
    Kiang, A., Hartman, Z. C., Liao, S., Xu, F., Serra, D., Palmer, D. J., Ng, P., & Amalfitano, A. (2006). Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Molecular Therapy : the Journal of the American Society of Gene Therapy, 13(1), 127-34.
    Kiang A, et al. Fully Deleted Adenovirus Persistently Expressing GAA Accomplishes Long-term Skeletal Muscle Glycogen Correction in Tolerant and Nontolerant GSD-II Mice. Mol Ther. 2006;13(1):127-34. PubMed PMID: 16169280.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. AU - Kiang,Anne, AU - Hartman,Zachary C, AU - Liao,Shaoxi, AU - Xu,Fang, AU - Serra,Delila, AU - Palmer,Donna J, AU - Ng,Philip, AU - Amalfitano,Andrea, Y1 - 2005/10/05/ PY - 2004/11/18/received PY - 2005/08/01/revised PY - 2005/08/01/accepted PY - 2005/9/20/pubmed PY - 2006/6/13/medline PY - 2005/9/20/entrez SP - 127 EP - 34 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 13 IS - 1 N2 - Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via nonviral regulatory elements (PEPCK promoter/ApoE enhancer) would facilitate long-term efficacy and decrease propensity to generate anti-hGAA antibody responses against hepatically secreted hGAA. Intravenous delivery of FDAdhGAA into GAA-tolerant or nontolerant GAA-KO mice resulted in long-term hepatic secretion of hGAA. Specifically, nontolerant mice achieved complete reversal of cardiac glycogen storage and near-complete skeletal glycogen correction for at least 180 days and tolerant mice for minimally 300 days coupled with the preservation of muscle strength. Anti-hGAA antibody levels in both mouse strains were significantly less relative to those previously generated by CMV-driven hGAA expression in nontolerant GAA-KO mice. However, plasma GAA levels decreased in nontolerant GAA-KO mice despite long-term intrahepatic GAA expression from the persistent vector. This intriguing result is discussed in light of other examples of "tolerance" induction by gene-transfer-based approaches. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/16169280/Fully_deleted_adenovirus_persistently_expressing_GAA_accomplishes_long_term_skeletal_muscle_glycogen_correction_in_tolerant_and_nontolerant_GSD_II_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(05)01554-6 DB - PRIME DP - Unbound Medicine ER -