Kijima H, Ishida H, Ohkawa T, Kashani-Sabet M, Scanlon K J
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA.
Pharmacol Ther. 1995;68(2):247-67. doi: 10.1016/0163-7258(95)02008-x.
The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expression because of their simple structure, sitespecific cleavage activity, and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against a myriad of genes, including oncogenes (ras, BCR-ABL, c-fos) and drug resistance genes, as well as the human immunodeficiency virus-type I genome. These ribozymes have cleaved the target RNAs in vitro and altered the cellular pathology. Currently, the therapeutic application of ribozymes to human diseases is limited by gene transfer systems. It is anticipated that ribozymes ultimately will play an important role in human gene therapy.
RNA 可被顺式或反式核酶（催化性 RNA，即 RNA 酶）切割这一发现具有潜在的重要治疗意义。自 20 世纪 80 年代被发现以来，核酶的生物化学特性和保守序列已得到充分表征。核酶因其结构简单、位点特异性切割活性和催化潜力，成为基因表达的有效调节剂。核酶介导的基因调节靶点范围广泛，从癌细胞到导致传染病的外源基因。核酶的其他靶点位点正处于开发和设计的初始阶段。核酶已被设计针对众多基因，包括癌基因（如 ras、BCR-ABL、c-fos）和耐药基因，以及人类免疫缺陷病毒 I 型基因组。这些核酶已在体外切割目标 RNA，并改变了细胞病理状态。目前，核酶在人类疾病治疗中的应用受到基因传递系统的限制。预计核酶最终将在人类基因治疗中发挥重要作用。
