Department of Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
BioDrugs. 1998 Jan;9(1):1-10. doi: 10.2165/00063030-199809010-00001.
Ribozymes have progressed from an intriguing subject of scientific study to therapeutic agents for the potential treatment of both acquired and inherited diseases. Clinical trials using ribozymes targeted against HIV, the aetiological agent of AIDS, have recently been initiated. Despite this rapid progression to clinical application, there are many unexplored avenues which still must be examined to improve the intracellular effectiveness of ribozymes. Since ribozymes are RNA molecules which selectively cleave RNA targets via base-pairing interactions, the rules governing nucleic acid hybridisation affect ribozyme function. In addition, knowledge of the cellular mechanisms governing RNA partitioning and stability apply equally to ribozymes as they do to the target RNAs. The successful therapeutic application of ribozymes depends upon increasing our knowledge of RNA metabolism and movement, and applying this knowledge in the design of ribozymes. This review summarises some of the progress and experimental approaches towards achieving these goals as well as surveying experimental testing of potential therapeutic applications. It is becoming increasingly evident that ribozymes can serve the dual function of a tool to elucidate the functional roles of many gene products as well as a therapeutic agent designed to functionally destroy deleterious RNAs.
核酶已经从一个有趣的科学研究课题发展成为治疗获得性和遗传性疾病的潜在治疗剂。最近已经开始了针对艾滋病病因 HIV 的靶向核酶的临床试验。尽管如此，要将核酶快速推进到临床应用还有许多未探索的途径，仍需对其进行检查以提高核酶的细胞内有效性。由于核酶是通过碱基配对相互作用选择性切割 RNA 靶标的 RNA 分子，因此控制核酸杂交的规则会影响核酶的功能。此外，控制 RNA 分配和稳定性的细胞机制的知识同样适用于核酶，就像它们适用于靶 RNA 一样。核酶的成功治疗应用取决于增加我们对 RNA 代谢和运动的了解，并将这些知识应用于核酶的设计中。这篇综述总结了在实现这些目标方面的一些进展和实验方法，并调查了潜在治疗应用的实验测试。越来越明显的是，核酶可以兼具工具和治疗剂的双重功能，既可以用来阐明许多基因产物的功能作用，也可以设计成功能性地破坏有害的 RNA。
