Production of human clotting Factor IX without toxicity in mice after vascular delivery of a lentiviral vector.
Nat Biotechnol
; 20(1): 53-7, 2002 Jan.
Article
em En
| MEDLINE
| ID: mdl-11753362
ABSTRACT
Replication-deficient lentiviral vectors (LV) have been shown to enable the stable genetic modification of multiple cell types in vivo. We demonstrate here that vascular and hepatic delivery of a third-generation HIV-derived lentiviral vector encoding human Factor IX (LV-hFIX) produced potentially therapeutic serum levels of hFIX protein with no vector-mediated local or systemic toxicity of adult mice. Portal vein administration produced the highest serum levels of hFIX and demonstrated proportionally higher levels of gene transfer to the liver with up to 4% of hepatocytes expressing hFIX. Vascular delivery of a lentiviral vector encoding GFP resulted in genetic modification of up to 12% of liver cells. Cell proliferation was not required for hepatocyte transduction with either vector. Serum hFIX levels reached 4% of normal levels following vascular LV-mediated hFIX gene transfer and remained stable for months following vector administration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator IX
/
Glicoproteínas de Membrana
/
Lentivirus
/
Vetores Genéticos
Limite:
Animals
Idioma:
En
Revista:
Nat Biotechnol
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos