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- Title
Site-specific genomic integration produces therapeutic Factor IX levels in mice.
- Authors
Olivares, Eric C.; Hollis, Roger P.; Chalberg, Thomas W.; Meuse, Leonard; Kay, Mark A.; Calos, Michele P.
- Abstract
We used the integrase from phage φC31 to integrate the human Factor IX (hFIX) gene permanently into specific sites in the mouse genome. A plasmid containing attB and an expression cassette for hFIX was delivered to the livers of mice by using high-pressure tail vein injection. When an integrase expression plasmid was coinjected, hFIX serum levels increased more than tenfold to ∼4 µg/ml, similar to normal FIX levels, and remained stable throughout the more than eight months of the experiment. hFIX levels persisted after partial hepatectomy, suggesting genomic integration of the vector. Site-specific integration was proven by characterizing and quantifying genomic integration in the liver at the DNA level. Integration was documented at two pseudo-attP sites, native sequences with partial identity to attP, with one site highly predominant. This study demonstrates in vivo gene transfer in an animal by site-specific genomic integration.
- Subjects
BLOOD coagulation factor IX; GENOMES; GENE therapy; PLASMIDS; MICE
- Publication
Nature Biotechnology, 2002, Vol 20, Issue 11, p1124
- ISSN
1087-0156
- Publication type
Article
- DOI
10.1038/nbt753