Prolonged transgene expression in murine salivary glands following non-primate lentiviral vector transduction.
Salivary glands are an accessible organ for gene therapy, enabling expression of recombinant proteins for both exocrine and endocrine secretion. Lentivirus-based vectors have many advantages for gene therapy, including their ability to infect nondividing cells and to stably integrate into the host genome, enabling long-term transgene expression without eliciting an inflammatory immune response. In the present study, murine salivary glands were inoculated with feline immunodeficiency virus (FIV)-based lentiviral vectors expressing various reporter genes. Luciferase expression was observed as early as 24 h posttransduction, peaked at 17-21 days, and remained stable for more than 80 days. Staining with X-gal suggested that mucous acinar cells were effectively transduced. FIV vector transduction with the secreted alkaline phosphatase gene increased serum levels in treated animals for up to 45 days, and the FIV vector harboring the interferon-gamma (IFN-gamma) expression cassette induced an increase in IFN-gamma serum levels as well as in the supernatant of salivary gland explant cultures. These results demonstrate that the transduction of salivary glands with nonprimate lentiviral vectors may provide a novel and highly effective vehicle for long-term endocrine transgene expression.
Shai
Ela
E
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Palmon
Aaron
A
Panet
Amos
A
Marmary
Yitzhak
Y
Sherman
Yoav
Y
Curran
Michael A
MA
Galun
Eithan
E
Condiotti
Reba
R
D000818:Animals; D003587:Cytomegalovirus / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D005822:Genetic Vectors; D007700:Kinetics; D016086:Lentivirus; D051379:Mice; D011401:Promoter Regions, Genetic; D012469:Salivary Glands / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic; D019076:Transgenes