Site-specific genomic integration produces therapeutic Factor IX levels in mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-11

AUTHORS

Eric C Olivares, Roger P Hollis, Thomas W Chalberg, Leonard Meuse, Mark A Kay, Michele P Calos

ABSTRACT

We used the integrase from phage phiC31 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 co-injected, hFIX serum levels increased more than tenfold to approximately 4 microg/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. More... »

PAGES

1124-1128

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nbt753

DOI

http://dx.doi.org/10.1038/nbt753

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031934701

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12379870


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