A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo
A novel allosterically trans-activated ribozyme, the maxizyme, with exceptional specificity in vitro and in vivo
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DOI：
10.1016/s1097-2765(00)80160-4
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发表时间：
1998-11-01
期刊：
影响因子：
16
通讯作者：
Taira, K
中科院分区：
文献类型：
--
作者：
Kuwabara, T;Warashina, M;Taira, K
我们构建了一种变构可控的新型酶（命名为maxizyme），它可以在人类tRNA（Val）启动子的控制下在体内转录。maxizyme具有可以识别目标序列的传感器臂，并且仅在存在这样的目标序列时，它可以形成一个可以捕获催化不可或缺的Mg2+离子的空腔。作为证明maxizyme潜在效用的靶标，我们选择了BCR-ABL mRNA，其翻译产物导致慢性髓性白血病。只有最大酶（而不是传统的核酶）具有极高的特异性和高水平的活性，不仅在体外，而且在培养细胞中，包括来自费城染色体患者的BV173细胞。maxizyme仅在具有该染色体的白血病细胞中诱导细胞凋亡。
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.