Pseudoknot interaction-mediated activation of hammerhead ribozyme which is applicable to gene-therapeutic agents
Pseudoknot interaction-mediated activation of hammerhead ribozyme which is applicable to gene-therapeutic agents
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假结相互作用介导的锤头核酶激活，适用于基因治疗剂
DOI：
10.1080/15257770.2014.887098
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
and Yoshiyuki Tanaka
中科院分区：
文献类型：
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作者：
Mituhiro Kuriyama;Yoshinori Kondo;and Yoshiyuki Tanaka
最近发现的通过假结相互作用（环之间的沃森-克里克碱基对）激活的锤头核酶是作为基因治疗剂的有吸引力的候选者，因为基因治疗核酶的序列可以简单地基于与靶RNA的序列互补性来设计。在此，我们检查了新发现的具有 I 型拓扑结构的假结型锤头核酶是否通过假结相互作用被激活。将假结序列替换为完全错配的假结序列显着降低了I型假结型锤头核酶的活性，而那些具有完全匹配的假结序列的活性则很高。结果表明，假结相互作用激活了 I 型假结型锤头核酶，使其适合作为基因治疗剂。
Recently discovered hammerhead ribozymes that are activated through pseudoknot interactions (Watson-Crick base pairs between loops) are attractive candidates as gene-therapeutic agents because sequences of gene-therapeutic ribozymes can be designed simply based on the sequence complementarity against target RNAs. Herein, we examined if the newly found pseudoknot-type hammerhead ribozyme with type I topology is activated through the pseudoknot interactions. Substitutions of pseudoknot sequences into fully mismatched ones significantly reduced the activity of type I pseudoknot-type hammerhead ribozyme, while those with full-matched pseudoknot sequences were highly active. The results indicated that the pseudoknot interactions activated type I pseudoknot-type hammerhead ribozyme, making them suitable as gene-therapeutic agents.