Scarborough Robert J, Gatignol Anne
Department of Microbiology and Immunology, McGill University, 3999 Cote Ste Catherine Street, Montreal, QC, Canada, H3T 1E2.
Adv Exp Med Biol. 2015;848:97-116. doi: 10.1007/978-1-4939-2432-5_5.
Ribozymes are structured RNA molecules that act as catalysts in different biological reactions. From simple genome cleaving activities in satellite RNAs to more complex functions in cellular protein synthesis and gene regulation, ribozymes play important roles in all forms of life. Several naturally existing ribozymes have been modified for use as therapeutics in different conditions, with HIV-1 infection being one of the most studied. This chapter summarizes data from different preclinical and clinical studies conducted to evaluate the potential of ribozymes to be used in HIV-1 therapies. The different ribozyme motifs that have been modified, as well as their target sites and expression strategies, are described. RNA conjugations used to enhance the antiviral effect of ribozymes are also presented and the results from clinical trials conducted to date are summarized. Studies on anti-HIV-1 ribozymes have provided valuable information on the optimal expression strategies and clinical protocols for RNA gene therapy and remain competitive candidates for future therapy.
核酶是在不同生物反应中起催化剂作用的结构化RNA分子。从卫星RNA中简单的基因组切割活性到细胞蛋白质合成和基因调控中更复杂的功能，核酶在所有生命形式中都发挥着重要作用。几种天然存在的核酶已被修饰用于不同病症的治疗，其中HIV-1感染是研究最多的病症之一。本章总结了为评估核酶用于HIV-1治疗的潜力而进行的不同临床前和临床研究的数据。描述了已被修饰的不同核酶基序，以及它们的靶位点和表达策略。还介绍了用于增强核酶抗病毒作用的RNA缀合物，并总结了迄今为止进行的临床试验结果。对抗HIV-1核酶的研究为RNA基因治疗的最佳表达策略和临床方案提供了有价值的信息，并且仍然是未来治疗的有力候选者。
