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Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4084-8. Epub 2001 Mar 13.

Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle.

Song S, Laipis PJ, Berns KI, Flotte TR.

Source

Genetics Institute, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA.

Abstract

We report here that the DNA-dependent protein kinase (DNA-PK) affects the molecular fate of the recombinant adeno-associated virus (rAAV) genome in skeletal muscle. rAAV-human alpha1-antitrypsin (rAAV-hAAT) vectors were delivered by intramuscular injection to either C57BL/6 (DNA-PKcs(+)) or C57BL/6-SCID [severe combined immunodeficient (SCID), DNA-PKcs(-)] mice. In both strains, high levels of transgene expression were sustained for up to 1 year after a single injection. Southern blot analysis showed that rAAV genomes persisted as linear episomes for more than 1 year in SCID mice, whereas only circular episomal forms were observed in the C57BL/6 strain. These results indicate that DNA-PK is involved in the formation of circular rAAV episomes.

PMID:: 11274433; [PubMed - indexed for MEDLINE]
PMCID:: PMC31183

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