The novel ribozyme, maxyzime, that inhibites leukemia progression in disease mouse

We have constructed an allosterically controllable novel enzyme (designared maxizyme) that can be transcribed in vivo under the control of a human tRNAVal promoter. The maxizyme has sensor arms that can recognize target sequences, and in the presence of such a target sequence only, it can from a cavity that cancapture 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. We have also found that this ribozyme complately inhibits tumor-cell infiltration in mice disease model.

ribozyme

maxizyme

bcr-abl

leukemia