RIBOZYMES AS POTENTIAL ANTI-HIV-1 THERAPEUTIC AGENTS
RIBOZYMES AS POTENTIAL ANTI-HIV-1 THERAPEUTIC AGENTS
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DOI：
10.1126/science.2107573
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发表时间：
1990-03-09
期刊：
影响因子：
56.9
通讯作者：
ROSSI, JJ
中科院分区：
文献类型：
--
作者：
SARVER, N;CANTIN, EM;ROSSI, JJ
某些RNA分子，称为核酶，具有酶的自我切割活性。裂解反应是催化性的，不需要能源。在植物RNA病原体中鉴定了“锤头”基序的核酶。这些核酶具有独特的二级（和可能的三级）结构，对它们的切割能力至关重要。本研究表明，精确切割人类免疫缺陷病毒1型（HIV-1）的序列在无细胞系统的锤头状核酶。除了无细胞研究之外，已经构建了稳定表达靶向HIV-1 gag转录物的锤头状核酶的人细胞。当这些细胞用HIV-1攻击时，观察到HIV-1 gag RNA的水平相对于非核酶表达细胞中的水平显著降低。gag RNA的减少反映在抗原p24水平的降低中。这些结果表明开发核酶作为抗人类病原体如HIV-1的治疗剂的可行性。
Certain RNA molecules, called ribozymes, possess enzymatic, self-cleaving activity. The cleavage reaction is catalytic and no energy source is required. Ribozymes of the "hammerhead" motif were identified in plant RNA pathogens. These ribozymes possess unique secondary (and possibly tertiary) structures critical for their cleavage ability. The present study shows precise cleavage of human immunodeficiency virus type 1 (HIV-1) sequences in a cell-free system by hammerhead ribozymes. In addition to the cell-free studies, human cells stably expressing a hammerhead ribozyme targeted to HIV-1 gag transcripts have been constructed. When these cells were challenged with HIV-1, a substantial reduction in the level of HIV-1 gag RNA relative to that in nonribozyme-expressing cells, was observed. The reduction in gag RNA was reflected in a reduction in antigen p24 levels. These results suggest the feasibility of developing ribozymes as therapeutic agents against human pathogens such as HIV-1.