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Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease.

Publication ,  Journal Article
Sun, B; Li, S; Bird, A; Koeberl, DD
Published in: Gene Ther
December 2010

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.

Duke Scholars

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Published In

Gene Ther

DOI

EISSN

1476-5462

Publication Date

December 2010

Volume

17

Issue

12

Start / End Page

1500 / 1505

Location

England

Related Subject Headings

  • Promoter Regions, Genetic
  • Perfusion
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Infusions, Intravenous
  • Humans
  • Hindlimb
  • HEK293 Cells
 

Citation

APA
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ICMJE
MLA
NLM
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 Ther, 17(12), 1500–1505. https://doi.org/10.1038/gt.2010.109
Sun, B., S. Li, A. Bird, and D. D. Koeberl. “Hydrostatic isolated limb perfusion with adeno-associated virus vectors enhances correction of skeletal muscle in Pompe disease.Gene Ther 17, no. 12 (December 2010): 1500–1505. 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, vol. 17, no. 12, Dec. 2010, pp. 1500–05. Pubmed, doi:10.1038/gt.2010.109.

Published In

Gene Ther

DOI

EISSN

1476-5462

Publication Date

December 2010

Volume

17

Issue

12

Start / End Page

1500 / 1505

Location

England

Related Subject Headings

  • Promoter Regions, Genetic
  • Perfusion
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Infusions, Intravenous
  • Humans
  • Hindlimb
  • HEK293 Cells