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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.

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 available

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 -