Vol.56 No.5 September 2008
Disordered cell-specific gene regulation system for suicide gene therapy
1)Department of Microbiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
2)CREST, Japan Science and Technology Agency
Abstract
Suicide gene therapy with the herpes simplex virus thymidine kinase(HSVtk) and ganciclovir(GCV) have shed light on the cancer gene therapy. However, a serious concern arose on account of the expression of HSVtk in normal cells, which can induce cytotoxicity. Here, we propose a novel strategy called D-RECS (drug or gene delivery system responding to cellular signals) for the development of a target cell-specific gene expression system. Polymers carrying the peptide substrate specific for each kinase (IκB kinase, Protein kinase Cα, and Src kinase) were prepared as the gene carriers. The results of the biochemical analyses revealed that the gene carriers enabled regulation of the gene expression in response to extraordinary activated kinase signals. This strategy represents an improvement of the technique of suicide gene therapy.
Key word
gene delivery, gene therapy, ganciclovir, herpes simplex virus thymidine kinase, biotechnology
Received
February 21, 2008
Accepted
June 25, 2008
Jpn. J. Chemother. 56 (5): 538-542, 2008
