Pharmacokinetic considerations regarding non-viral cancer gene therapy.

Cancer gene therapy, in which pharmacologically active compounds are administered to cancer patients in a genetic form, has been examined not only in animals but also in cancer patients. Viral vector-induced severe side effects in patients have greatly underscored the importance of non-viral gene transfer methods. Even though the importance of pharmacokinetics is undoubtedly understood in the development of anticancer therapies, its importance has been less well recognized in non-viral cancer gene therapy. When transgene products express their activity within transduced cells, such as herpes simplex virus type 1 thymidine kinase and short hairpin RNA, the pharmacokinetics of the vectors and the expression profiles of the transgenes will determine the efficacy of gene transfer. The percentage of cells transduced is highly important if few by-stander effects are expected. If transgene products are secreted from cells into the blood circulation, such as interferons and interleukins, the pharmacokinetics of transgenes becomes a matter of significant importance. Then, any approach to increasing the level and duration of transgene expression will increase the therapeutic effects of cancer gene therapy. Here we review the pharmacokinetics of both non-viral vectors and transgene products, and discuss what should be done to achieve safer and more effective non-viral cancer gene therapy.