Site-specific genomic integration produces therapeutic Factor IX levels in mice.

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Olivares EC,Hollis RP,Chalberg TW,Meuse L,Kay MA,Calos MP

doi

10.1038/nbt753

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

1124-8

issue

11

eissn

1087-0156

issn

1546-1696

pii

nbt753

journal_volume

20

pub_type

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