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Scientists have long toyed with the idea of putting to work a special class of biological catalysts, called ribozymes, as therapeutic agents. These molecular scissors would harness the activities of overly active genes that contribute to diseases like cancer by cutting their immediate products, messenger RNAs, into unusable pieces. The advantage of this approach, is that these molecules can be made to recognize very specific targets. This is reported in this month issue of EMBO reports.
Up until now, however, technical difficulties have hampered the development of such tools; the targets for these molecules are often folded extensively, making particular cleavage sites inaccessible to the catalyst. However, in the May 15 issue of EMBO reports, H. Kawasaki and K. Taira report on a technical breakthrough. By linking ribozymes to helicases, cellular components whose normal function is to 'smooth out' folded RNA's to allow them to be 'translated' into proteins, these investigators have managed to circumvent this 'folding' difficulty. They have been able to efficiently inhibit the activities of a number of target RNA's, even at sites that are known to be inaccessible to regular ribozymes. This has further allowed them to develop a method for investigating the functions of random RNA's, creating a tool that may be invaluable in characterizing the functions of many of the previously unknown genes that have only recently been uncovered by various genome projects. Although we are not yet ready to treat any diseases using ribozymes, this study may indeed be a big step in the right direction.
(Text: Christine M. Blaumueller)
Reference
Identification of genes by hybrid ribozymes that couple cleavage activity with the unwinding activity of an endogenous RNA helicase
Hiroaki Kawasaki and Kazunari Taira+
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Gene Discovery Research Center, National Institute of Advanced Industrial Science and Technology (AIST) and GenoFunction, Inc., Central 4, 1-1-1 Higashi, Tsukuba Science City 305-8562, Japan
Corresponding author at: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Tokyo 113-8656, Japan. Tel: +81 3 5841 8828; Fax: +81 3 5841 8828; E-mail: taira@chembio.t.u-tokyo.ac.jp
http://www.embo-reports.oupjournals.org/cgi/content/short/3/5/443
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