title: A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo.
abstract: We have constructed an allosterically controllable novel enzyme (designated maxizyme) that can be transcribed in vivo under the control of a human tRNA(Val) promoter. The maxizyme has sensor arms that can recognize target sequences, and in the presence of such a target sequence only, it can form a cavity that can capture catalytically indispensable Mg2+ ions. As a target for a demonstration of the potential utility of the maxizyme, we chose BCR-ABL mRNA, the translated products of which cause chronic myelogenous leukemia. Only the maxizyme (but not conventional ribozymes) had extremely high specificity and high-level activity, not only in vitro but also in cultured cells including BV173 cells derived from a patient with a Philadelphia chromosome. The maxizyme induced apoptosis only in leukemic cells with this chromosome.
authors.affiliation: National Institute for Advanced Interdisciplinary Research, Tsukuba Science City, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuwabara
authors.forename: M
authors.initials: M
authors.lastname: Warashina
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: K
authors.initials: K
authors.lastname: Tani
authors.forename: S
authors.initials: S
authors.lastname: Asano
authors.forename: K
authors.initials: K
authors.lastname: Taira
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004792:Enzyme Precursors / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009690:Nucleic Acid Conformation; D010677:Philadelphia Chromosome; D016337:RNA, Catalytic / Q000378:metabolism* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism*; D012366:RNA, Transfer, Val / Q000235:genetics; D013379:Substrate Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004792:Enzyme Precursors; D007377:Interleukin-3; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012366:RNA, Transfer, Val; D016044:Fusion Proteins, bcr-abl; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D008274:Magnesium