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Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease.
Gene Ther. 2010 Dec; 17(12):1500-5.GT

Abstract

Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle-specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP administration of AAV2/8 vectors encoding alkaline phosphatase or human GAA-transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1 × 10¹¹), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3 × 10¹⁰) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high-level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers.

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 available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20686508

Citation

Sun, B, et al. "Hydrostatic Isolated Limb Perfusion With Adeno-associated Virus Vectors Enhances Correction of Skeletal Muscle in Pompe Disease." Gene Therapy, vol. 17, no. 12, 2010, pp. 1500-5.
Sun B, Li S, Bird A, et al. Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease. Gene Ther. 2010;17(12):1500-5.
Sun, B., Li, S., Bird, A., & Koeberl, D. D. (2010). Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease. Gene Therapy, 17(12), 1500-5. https://doi.org/10.1038/gt.2010.109
Sun B, et al. Hydrostatic Isolated Limb Perfusion With Adeno-associated Virus Vectors Enhances Correction of Skeletal Muscle in Pompe Disease. Gene Ther. 2010;17(12):1500-5. PubMed PMID: 20686508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease. AU - Sun,B, AU - Li,S, AU - Bird,A, AU - Koeberl,D D, Y1 - 2010/08/05/ PY - 2010/8/6/entrez PY - 2010/8/6/pubmed PY - 2011/5/20/medline SP - 1500 EP - 5 JF - Gene therapy JO - Gene Ther VL - 17 IS - 12 N2 - Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the inherited deficiency of acid-α-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. We hypothesized that hydrostatic isolated limb perfusion (ILP) administration of an adeno-associated virus (AAV) vector containing a muscle-specific promoter could achieve relatively higher transgene expression in the hindlimb muscles of GAA-knockout (GAA-KO) mice, in comparison with intravenous (IV) administration. ILP administration of AAV2/8 vectors encoding alkaline phosphatase or human GAA-transduced skeletal muscles of the hindlimb widely, despite the relatively low number of vector particles administered (1 × 10¹¹), and IV administration of an equivalent vector dose failed to transduce skeletal muscle detectably. Similarly, ILP administration of fewer vector particles of the AAV2/9 vector encoding human GAA (3 × 10¹⁰) transduced skeletal muscles of the hindlimb widely and significantly reduced glycogen content to, in comparison with IV administration. The only advantage for IV administration was moderately high-level transduction of cardiac muscle, which demonstrated compellingly that ILP administration sequestered vector particles within the perfused limb. Reduction of glycogen storage in the extensor digitorum longus demonstrated the potential advantage of ILP-mediated delivery of AAV vectors in Pompe disease, because type II myofibers are resistant to enzyme replacement therapy. Thus, ILP will enhance AAV transduction of multiple skeletal muscles while reducing the required dosages in terms of vector particle numbers. SN - 1476-5462 UR - https://www.unboundmedicine.com/medline/citation/20686508/Hydrostatic_isolated_limb_perfusion_with_adeno_associated_virus_vectors_enhances_correction_of_skeletal_muscle_in_Pompe_disease_ L2 - https://doi.org/10.1038/gt.2010.109 DB - PRIME DP - Unbound Medicine ER -