Recombinant adeno-associated virus derived vectors (rAAV2) efficiently transduce ovarian and hepatocellular carcinoma cells--implications for cancer gene therapy.
Recombinant adeno-associated virus vectors (rAAV) represent a most promising gene delivery vehicles for gene therapy applications because their unique properties, such as capability to infect both proliferating and non proliferating cells of broad host range, and possibilities of long-term expression and site-specific integration. rAAV are also described as vectors neither toxic nor pathogenic to the cells. rAAV vectors are also thought to be attractive for cancer gene therapy. Here, we used rAAV2 vectors encoding reporter genes, rAAV/GFP and rAAV/LacZ to transduce cancer cells. The rAAV preparations were produced by a transient triple AAV plasmid transfection of AAV-293 packaging cells and isolated/purified by iodixanol-gradient method. We report a different rAAV transduction efficiency of the two cancer cell lines cells--ovarian carcinoma (OVP 10) and hepatocellular carcinoma (C3A) cells. The expression of the reporter genes due to rAAV uptake was about two fold higher for ovarian cells than for hepatocellular cells. Our studies have also revealed the long-term expression of GFP gene in hepatocellular (C3A) rAAV/GFP transduced cells. These findings indicate that adeno-associated virus derived vectors could be very useful for cancer gene therapy applications, however, further investigations of the mechanisms of rAAV gene delivery are still needed.
Małecki
Maciej
M
Department of Cell Biology, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Warsaw, Poland. mahan@poczta.wp.pl
Swoboda
Paweł
P
Pachecka
Jan
J
D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods*
D049452:Green Fluorescent Proteins