Site-specific genomic integration produces therapeutic Factor IX levels in mice.
Nat Biotechnol
; 20(11): 1124-8, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12379870
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fator IX
/
Mutagênese Sítio-Dirigida
/
Fígado
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article