© 2002 by Oxford University Press
Construction of an allosteric trans-maxizyme targeting for two distinct oncogenes
1 Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan, 2 Gene Function Research Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan
A maxizyme is dimmer of minimized ribozymes (minizymes) and can specifically cleave two target sites. The maxizyme also can allosterically cleave the target RNA only when it recognizes two target sites. In this study, for a cancer gene therapy, we focused two distinct oncogenes, cyclinD1 and hst-1, which are overexpressed in breast cancer cells. If we use conventional ribozymes for suppression of expression of those genes, these ribozymes affect not only these mRNAs in cancer cells but also those in normal cells because those genes are necessary for a growth factor-dependent signal transduction and a cell cycle in normal cells. To overcome this problem, we tried to design the trans-maxizyme that can cleave these mRNAs only in the breast cancer cells.