Gene therapy approach in renal disease in the 21st century

Theoretically, gene therapy has distinct potential to treat renal disease at the most fundamental level. However, the ability to pursue gene therapy has been limited by the availability of an adequate system for gene delivery to the kidney. The present viral vector systems seem to have limitations for clinical use because of uncertainty regarding their toxicity and immunogenicity; however, adenovirus-mediated gene transfer succeeded in gene expression in the kidney. Adeno-associated virus has a potential to be utilized as a vector targeting both kidney and skeletal muscle. Given that the systemic delivery of the functional protein can serve for the therapy of the renal diseases, skeletal muscle targeting gene therapy might be an alternative strategy for treatment of renal disease. Non-viral vectors such as the haemagglutinating virus of Japan (HVJ)-liposome method and cationic liposome are possibilities, but their efficiency needs to be improved. Electric pulse is emerging as a new and less harmful strategy of gene transfer to various tissues, including the kidney. I believe that two plausible strategies exist for the therapeutic use of gene transfer in the near future: skeletal muscle-targeting gene therapy and kidney transplantation. Application of gene therapy to the transplanted kidney may potentially improve graft outcome by reducing acute and chronic rejections. The emerging strategies of gene transfer in kidneys are reviewed and the potential application of gene therapy in renal diseases are discussed.