Maxizymes, novel allosterically controllable ribozymes, can be designed to cleave various substrates.
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.
Tanabe
T
T
Department of Hepatology/Oncology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8539.
Takata
I
I
Kuwabara
T
T
Warashina
M
M
Kawasaki
H
H
Tani
K
K
Ohta
S
S
Asano
S
S
Taira
K
K
D001345:Autoradiography; D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases / Q000737:chemistry; D008967:Molecular Biology; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012313:RNA / Q000138:chemical synthesis; D016337:RNA, Catalytic / Q000737:chemistry*; D013379:Substrate Specificity
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016337:RNA, Catalytic; D012313:RNA; D020558:GTP Phosphohydrolases