Light-induced adenovirus gene transfer, an efficient and specific gene delivery technology for cancer gene therapy.
A main issue for further clinical progress of cancer gene therapy is to develop technologies for efficient and specific delivery of therapeutic genes to tumor cells. In this work, we describe a photochemical treatment that substantially improves gene delivery by adenovirus, one of the most efficient gene delivery vectors known. Transduction of two different cell lines was studied by microscopy, flow cytometry, and an enzymatic assay, employing a beta-galactosidase-encoding adenovirus. The photochemical treatment induced a >20-fold increase in gene transduction, compared with conventional adenovirus infection, both when measured as the percentage of cells transduced, and when measured as the total beta-galactosidase activity in the cell population. The effect was most pronounced at lower virus doses, where in some cases the same transduction efficiency could be achieved with a 20 times lower virus dose than with conventional infection. Photochemical treatments are already in clinical use for cancer therapy, and generally are very specific and have few side effects. The photochemical internalization technology described thus has a clear potential for improving both the efficiency and the specificity of gene delivery in cancer gene therapy, making it possible to achieve efficient site-specific in vivo gene delivery by adenoviral vectors.
Høgset
Anders
A
PCI Biotech AS, N-0377 Oslo, Norway. anders.hogset@pcibiotech.no
Engesaeter
Birgit Ovstebø
BO
Prasmickaite
Lina
L
Berg
Kristian
K
Fodstad
Oystein
O
Maelandsmo
Gunhild Mari
GM
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008027:Light; D009942:Organometallic Compounds / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000528:radiation effects* / Q000821:virology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C064331:aluminum phthalocyanine disulfonate; D001616:beta-Galactosidase