Novel cGMP liposomal vectors mediate efficient gene transfer

Abstract

Viral vector systems are the most commonly used gene transfer tools for clinical gene therapy. However, lipofection systems are potential alternatives because of lower immunogenicity and easier cGMP production, but in vivo stability and transduction efficacy need to be improved. Therefore, we investigated gene transduction efficiency of our novel cGMP cationic lipids, CCQ22 and CCQ32, by FACS analysis. Toxicity analysis was performed to determine the cytotoxic side effects of the novel lipids. To evaluate the stability of the compounds in the context of local delivery to patients with intraperitoneally metastatic ovarian cancer, gene transfer was also tested in the presence of malignant ascites. Our novel cGMP standard lipids mediated gene transfer rates of more than 50%. However, for most cell lines cytotoxic side effects were similar to our reference lipofection system. In general, ascites had no major influence on gene transduction rates with the novel lipids. Our results suggest that CCQs may compare favorably with commercially available lipofection systems. These promising results facilitate further analysis of the compounds.

Combined Liposome-Mediated Cytosine Deaminase Gene Therapy with Radiation in Killing Rectal Cancer Cells and Xenografts in Athymic Mice

“…These vector systems have a relatively high efficiency of transfection, but they also have several major limitations and even cause serious side effects on human body. Liposome-mediated gene transfer has several advantages over viral vector-mediated gene transfer systems (18,19). In particular, liposomes are not immunogenic and are safe for clinical use.…”