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Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector.

Publication ,  Journal Article
Sun, B; Chen, Y-T; Bird, A; Xu, F; Hou, Y-X; Amalfitano, A; Koeberl, DD
Published in: Mol Ther
April 2003

We have developed an improved method for packaging adeno-associated virus (AAV) vectors with a replication-defective adenovirus-AAV (Ad-AAV) hybrid virus. The AAV vector encoding human acid alpha-glucosidase (hGAA) was cloned into an E1, polymerase/preterminal protein-deleted adenovirus, such that it is packaged as an Ad vector. Importantly, the Ad-AAV hybrid cannot replicate during AAV vector packaging in 293 cells, because of deletion of polymerase/preterminal protein. The residual Ad-AAV in the AAV vector stock was reduced to <1 infectious particle per 10(10) AAV vector particles. These modifications resulted in approximately 30-fold increased packaging of the AAV vector for the hybrid Ad-AAV vector method as compared with standard transfection-only methods. Similarly improved packaging was demonstrated for pseudotyping the AAV vector as AAV6, and for AAV vector packaging with a second Ad-AAV vector encoding canine glucose-6-phosphatase. Liver-targeted delivery of either the Ad-AAV hybrid or AAV vector particles in acid alpha-glucosidase-knockout (GAA-KO) mice revealed secretion of hGAA with the Ad-AAV vector, and sustained secretion of hGAA with an AAV vector in hGAA-tolerant GAA-KO mice. Further development of hybrid Ad-AAV vectors could offer distinct advantages for gene therapy in glycogen storage diseases.

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Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

April 2003

Volume

7

Issue

4

Start / End Page

467 / 477

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Virus Assembly
  • Portal Vein
  • Mice, Knockout
  • Mice
  • Injections, Intravenous
  • Humans
  • Hela Cells
  • HeLa Cells
  • Glycogen Storage Disease Type II
 

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Sun, B., Chen, Y.-T., Bird, A., Xu, F., Hou, Y.-X., Amalfitano, A., & Koeberl, D. D. (2003). Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector. Mol Ther, 7(4), 467–477. https://doi.org/10.1016/s1525-0016(03)00022-4
Sun, Baodong, Y. -. T. Chen, Andrew Bird, Fang Xu, Yang-Xun Hou, Andrea Amalfitano, and Dwight D. Koeberl. “Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector.Mol Ther 7, no. 4 (April 2003): 467–77. https://doi.org/10.1016/s1525-0016(03)00022-4.
Sun, Baodong, et al. “Packaging of an AAV vector encoding human acid alpha-glucosidase for gene therapy in glycogen storage disease type II with a modified hybrid adenovirus-AAV vector.Mol Ther, vol. 7, no. 4, Apr. 2003, pp. 467–77. Pubmed, doi:10.1016/s1525-0016(03)00022-4.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

April 2003

Volume

7

Issue

4

Start / End Page

467 / 477

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Virus Assembly
  • Portal Vein
  • Mice, Knockout
  • Mice
  • Injections, Intravenous
  • Humans
  • Hela Cells
  • HeLa Cells
  • Glycogen Storage Disease Type II