title: Maxizyme technology.
abstract: Ribozymes are small and versatile nucleic acids that can cleave RNAs at specific sites. These molecules have great potential to be used as effective gene-therapeutic agents. However, because of the limitation for cleavable sequences within the target mRNA, in some cases conventional ribozymes have failed to exhibit precise cleavage specificity. A maxizyme is the dimer of minimized ribozymes (minizymes), which can specifically cleave two distinct target sites. The maxizyme also has an allosteric function in that it can form an active conformation and cleave the two target sites only when it recognizes two distinct target sites. We demonstrated previously that an allosterically controllable maxizyme was a powerful tool in the disruption of an abnormal chimeric RNA (bcr-abl) in cells and in mice. Furthermore, more than five custom-designed maxizymes have clearly demonstrated these allosteric functions in vitro and in vivo. Thus, maxizyme technology is not limited to one specific case, but may have broad general applicability in molecular biology and in molecular gene therapy.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Iyo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
mesh_terms: D000494:Allosteric Regulation; D001483:Base Sequence; D019281:Dimerization; D005822:Genetic Vectors; D007202:Indicators and Reagents; D007700:Kinetics; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D055503:Protein Multimerization; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism*; D034741:RNA, Small Interfering; D014158:Transcription, Genetic
chemical_list: D007202:Indicators and Reagents; D016337:RNA, Catalytic; D034741:RNA, Small Interfering; C427204:hammerhead ribozyme