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Perit Dial Int 26(6): 633-640 2006
© 2006 International Society for Peritoneal Dialysis
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TECHNOLOGICAL ADVANCES IN PERITONEAL DIALYSIS RESEARCH

GENE TRANSFER USING NONVIRAL DELIVERY SYSTEMS

Masanobu Miyazaki1,3, Yoko Obata1, Katsushige Abe1, Akira Furusu1, Takehiko Koji2, Yasuhiko Tabata4 and Shigeru Kohno1

1 Second Department of Internal Medicine,2 Department of Histology and Cell Biology, Nagasaki University School of Medicine;3 Miyazaki-Furukawa Clinic, Nagasaki;4 Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

Correspondence to: M. Miyazaki, Miyazaki-Furukawa Clinic, 3-12 Shiratori, Nagasaki 852-8042, Japan.
msnbmiya-ngs{at}umin.ac.jp

In peritoneal dialysis, loss of peritoneal function is a major factor in treatment failure. The alterations in peritoneal function are related to structural changes in the peritoneal membrane, including peritoneal sclerosis with increased extracellular matrix. Although peritoneal sclerosis is considered reversible to some extent through peritoneal rest, which improves peritoneal function and facilitates morphological changes, there has been no therapeutic intervention and no drug against the development and progression of peritoneal sclerosis. Using recent biotechnological advances in genetic engineering, a strategy based on genetic modification of the peritoneal membrane could be a potential therapeutic maneuver against peritoneal sclerosis and peritoneal membrane failure. Before this gene therapy may be applied clinically, a safe and effective gene delivery system as well as the selection of a gene therapy method must be established. There are presently two kinds of gene transfer vectors: viral and nonviral. Viral vectors are used mainly as a gene delivery system in the field of continuous ambulatory peritoneal dialysis research; however, they have several problems such as immunogenicity and toxicity. On the other hand, nonviral vectors have several advantages over viral vectors. We review here gene transfer using nonviral vector systems in the peritoneum: electroporation, liposomes, and cationized gelatin microspheres. In the field of peritoneal dialysis, gene therapy research using nonviral vectors is presently limited. Improvement in delivery methods together with an intelligent design of targeted genes has brought about large degrees of enhancement in the efficiency, specificity, and temporal control of nonviral vectors.

KEY WORDS: Peritoneal sclerosis; gene therapy; gene transfer; electroporation; liposomes; cationized gelatin microspheres.

Received 9 October 2005; accepted 15 August 2006.




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