药学学报, 2020, 55(2): 218-225
引用本文:
汤仙阁, 关晓多, 陈锐, 胡蓓. 寡核苷酸药物的临床药理学研究进展[J]. 药学学报, 2020, 55(2): 218-225.
TANG Xian-ge, GUAN Xiao-duo, CHEN Rui, HU Pei. Progress in clinical pharmacology of oligonucleotides[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 218-225.

寡核苷酸药物的临床药理学研究进展
汤仙阁, 关晓多, 陈锐, 胡蓓
北京协和医院临床药理研究中心, 创新药物临床PKPD研究北京市重点实验室, 北京 100032
摘要:
一些罕见、难治愈疾病仍然难以攻克,继化学小分子和单克隆抗体药物之后,寡核酸药物因其在RNA水平上调控疾病基因转录翻译的独特机制,有望填补空白治疗领域。此外最近3年FDA批准6个寡核酸药物,吸引制药行业广泛关注这个领域。作为新一类药物分子,寡核苷酸药物极性大、带电荷、需要借助化学修饰和递药系统改善成药性,因而具有不同于化学小分子和单抗药物的临床药理学特性,为临床早期研发带来新挑战。本文主要从寡核苷酸药物的技术发展、作用机制、人体药代动力学、药效和安全性的角度综述其特征。
关键词:    寡核苷酸      化学修饰      药物递送      药代动力学      药效      安全性     
Progress in clinical pharmacology of oligonucleotides
TANG Xian-ge, GUAN Xiao-duo, CHEN Rui, HU Pei
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Beijing 100032, China
Abstract:
Following small molecules and monoclonal antibodies, oligonucleotides are expected to overcome the rare and refractory human diseases. It has been attracted the attention of the pharmaceutical industry since the approval of six oligonucleotides in recent years because of their unique mechanism of regulating disease gene transcription at the RNA level. As a new class of drug molecules, oligonucleotides are highly polar, charged, and need to be improved by means of chemical modification and drug delivery systems. And therefore, they have different clinical pharmacology properties compared with chemical molecules and monoclonal antibodies, which pose new challenges for early clinical development. This paper reviews the characteristics of oligonucleotides from the perspective of technological development, mechanism of action, human pharmacokinetics, efficacy and safety.
Key words:    oligonucleotides    chemical modification    drug delivery    pharmacokinetics    efficacy    safety   
收稿日期: 2019-10-23
DOI: 10.16438/j.0513-4870.2019-0834
基金项目: 中国医学科学院医学与健康科技创新工程经费资助(2016-I2M-1-010).
通讯作者: 陈锐,Tel:86-10-69158367,E-mail:chenrui04@126.com;胡蓓,Tel:86-10-69158366,E-mail:hubei01_pumch@163.com
Email: chenrui04@126.com;hubei01_pumch@163.com
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