Probing of the secondary structure of maxizymes

Zhou, Jinchuan; Nakamatsu, Yuka; Kuwabara, Tomoko; Warashina, Masaki; Tanaka, Yoshiyuki; Yoshinari, Koichi; Taira, Kazunari

doi:10.1093/nass/42.1.219

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“…We demonstrated that the activity of this maxizyme could be controlled allosterically not only in vitro but also in cultured cells by the presence of the junction in BCR-ABL (b2a2) mRNA . We confirmed the secondary structure of this maxizyme by studies with enzymatic and chemical probes 2 Types of hypothetical splicing and possible sites of cleavage within normal mRNA and abnormal mRNA by wild-type ribozymes.…”

Section: Introductionsupporting

confidence: 52%

“…24 We confirmed the secondary structure of this maxizyme by studies with enzymatic and chemical probes. 49 The adjustable sequences in maxizymes correspond to the sensor arms and the common stem II. At first glance, the design of allosterically controllable constructs seems rather complicated and we cannot exclude the possibility that our initial success was an accident based on some serendipitous features of the sequence of interest.…”

Section: Introductionmentioning

confidence: 99%

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Maxizymes, Novel Allosterically Controllable Ribozymes, Can Be Designed To Cleave Various Substrates

et al. 2000

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We demonstrated previously that an allosterically controllable novel ribozyme, designated the maxizyme, is a powerful tool for disruption of an abnormal chimeric RNA target [BCR-ABL (b2a2) mRNA], and we proposed that it might provide the basis for future gene therapy for the treatment of chronic myelogenous leukemia (Kuwabara et al. Mol. Cell 1998, 2, 617-627). The maxizyme has sensor arms that can recognize a specific sequence and, in the presence exclusively of such a specific sequence, it can form a cavity for capture of catalytically indispensable Mg2+ ions. Cleavage of the target RNA then occurs at a site distant from the specific sequence. Clearly, the specific sequences recognized by sensor arms should not be limited to those of the above mentioned abnormal chimeric target. Thus, to demonstrate the general applicability of maxizyme technology, we constructed maxizymes targeted to other mRNAs, such as PML-RAR alpha mRNA, sDLST mRNA, and BCR-ABL (b1a2) mRNA, that are not cleaved with high specificity by the wild-type hammerhead ribozyme. Specific and efficient cleavage in vitro of these mRNAs by the custom-designed maxizymes demonstrated clearly that maxizyme technology is not limited to a specific case but may have broad general applicability in molecular biology and, also, in a clinical setting.

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Section: Introductionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%