Adenovirus-mediated hepatic gene transfer in mice: comparison of intravascular and biliary administration.
Hum Gene Ther
; 7(14): 1693-9, 1996 Sep 10.
Article
em En
| MEDLINE
| ID: mdl-8886840
ABSTRACT
Recombinant adenoviruses have received much attention as a potential vector for gene therapy because of their ability to transduce many cell types with high efficiencies in vivo. After intravenous infusion, the majority of the vector is found in hepatocytes, but vector DNA is found to varying degrees in other tissues. In an attempt to restrict adenovirus-mediated gene transfer to the liver, we developed a microsurgical method that allowed for vector administration directly into the biliary tract of a mouse. We demonstrate that gene transfer was 4- to 10-fold more restricted to the liver after biliary tract infusion than after intravascular infusion. Intravascular infusion of recombinant adenovirus elicits a powerful immune response that limits gene expression and the ability to readminister the vector. Biliary infusion resulted in a slightly lesser immune response as determined by the lower neutralizing antibody titers directed against the vector compared with animals treated by intravascular infusion. There was no difference in the persistence of gene expression, suggesting a similar cell-mediated immune response against the vector containing cells in animals administered vector by either method. As future-generation adenovirus vectors that are safer and less immunogenic become available, the more liver specific gene transfer via the biliary tract may offer advantages over intravenous infusion for hepatic gene therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Biliar
/
Adenoviridae
/
Técnicas de Transferência de Genes
/
Vetores Genéticos
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Hum Gene Ther
Ano de publicação:
1996
Tipo de documento:
Article