Prolonged liver-specific transgene expression by a non-primate lentiviral vector.
Liver-directed gene therapy has the potential for treatment of numerous inherited diseases affecting metabolic functions. The aim of this study was to evaluate gene expression in hepatocytes using feline immunodeficiency virus-based lentiviral vectors, which may be potentially safer than those based on human immunodeficiency virus. In vitro studies revealed that gene expression was stable for up to 24 days post-transduction and integration into the host cell genome was suggested by Alu PCR and Southern blot analyses. Systemic in vivo administration of viral particles by the hydrodynamics method resulted in high levels of gene expression exclusively in the liver for over 7 months whereas injection of plasmid DNA by the same method led to transient expression levels. Our studies suggest that feline immunodeficiency-based lentiviral vectors specifically transduce liver cells and may be used as a novel vehicle of gene delivery for treatment of metabolic disease.
Condiotti
Reba
R
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem 91120, Israel. reba@hadassah.org.il
Curran
Michael A
MA
Nolan
Garry P
GP
Giladi
Hilla
H
Ketzinel-Gilad
Mali
M
Gross
Eitan
E
Galun
Eithan
E
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002415:Cats; D045744:Cell Line, Tumor; D016181:Feline Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000821:virology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics*; D017969:Lentiviruses, Feline / Q000235:genetics; D011323:Primates; D014162:Transfection / Q000379:methods*; D019076:Transgenes / Q000235:genetics