Stull R A, Szoka F C
Department of Pharmacy, University of California, San Francisco 94143-0446, USA.
Pharm Res. 1995 Apr;12(4):465-83. doi: 10.1023/a:1016281324761.
Nucleic acids are increasingly being considered for therapeutic uses, either to interfere with the function of specific nucleic acids or to bind specific proteins. Three types of nucleic acid drugs are discussed in this review: aptamers, compounds which bind specific proteins; triplex forming (antigene) compounds; which bind double stranded DNA; and ribozymes (catalytic RNA), which bind and cleave RNA targets. The binding of aptamers to protein may involve specific sequence recognition, although this is not always the case. The interaction of triplex forming oligonucleotides or ribozymes with their targets always involves specific sequence recognition and hybridization. Early optimism concerning the possibility of designing drugs without a priori knowledge of the structure of the target (except a nucleotide sequence) has been tempered by the finding that target structure has a dramatic effect upon the hybridization potential of the nucleic acid drug. Other obstacles to the creation of effective nucleic acid drugs are their relative high molecular weight (> 3300) and their sensitivity to degradation. The molecular weight of these compounds has created a significant delivery problem which needs to be solved if nucleic acid drugs are to become effective therapies.
核酸越来越多地被考虑用于治疗用途，要么干扰特定核酸的功能，要么结合特定蛋白质。本文综述了三种类型的核酸药物：适体，即结合特定蛋白质的化合物；三链形成（反基因）化合物，其结合双链DNA；以及核酶（催化RNA），其结合并切割RNA靶标。适体与蛋白质的结合可能涉及特定序列识别，尽管并非总是如此。三链形成寡核苷酸或核酶与其靶标的相互作用总是涉及特定序列识别和杂交。早期对于在无需先验了解靶标结构（除核苷酸序列外）的情况下设计药物可能性的乐观态度，因发现靶标结构对核酸药物的杂交潜力有显著影响而有所缓和。开发有效核酸药物的其他障碍包括其相对较高的分子量（>3300）以及对降解的敏感性。这些化合物的分子量造成了一个重大的递送问题，如果核酸药物要成为有效的治疗方法，这个问题需要解决。
