药学学报, 2021, 56(9): 2335-2345
引用本文:
程忠哲, 姜宏梁. 核酸药物生物分析方法研究进展[J]. 药学学报, 2021, 56(9): 2335-2345.
CHENG Zhong-zhe, JIANG Hong-liang. Advances in the bioanalysis of therapeutic oligonucleotides[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2335-2345.

核酸药物生物分析方法研究进展
程忠哲1, 姜宏梁2*
1. 潍坊医学院药学院, 山东 潍坊 261053;
2. 华中科技大学同济医学院药学院, 湖北 武汉 430030
摘要:
随着人们对疾病基因相关机制认识的不断深入,核酸药物因其在基因治疗中的潜在作用而引起广泛关注。目前核酸药物已成为生物医药发展的前沿领域。为支持核酸药物的药代/毒代动力学与药效学研究,推动新药开发,满足临床治疗药物监测的需求,核酸药物的生物分析方法得到了突飞猛进的发展。除传统的基于核酸分子杂交的酶联免疫法外,实时荧光定量PCR、基于液相色谱分离技术法等也展现出广阔的应用前景。这些分析技术各具特点,但也存在一定的局限性。本文简要综述近年来核酸药物生物分析技术的应用和发展趋势,以及在法规指导下的规范性核酸药物生物分析研究所面临的挑战及解决方案。
关键词:    核酸药物      生物分析      基因治疗      药代动力学     
Advances in the bioanalysis of therapeutic oligonucleotides
CHENG Zhong-zhe1, JIANG Hong-liang2*
1. School of Pharmacy, Weifang Medical University, Weifang 261053, China;
2. School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract:
Oligonucleotides have attracted the widespread attention in disease diagnosis and gene therapy. At present, the nucleic acid drugs are at the forefront of biomedical and pharmaceutical research. The bioanalysis of therapeutic oligonucleotides has been slow, however, due to the requirements for pharmacokinetic/toxicokinetic and pharmacodynamic studies in pharmaceutical development. Conventionally, the hybridization-enzyme linked immunosorbent assay (hybridization-ELISA) is widely used in the bioanalysis of therapeutic oligonucleotides. Recentlly, many technologies such as real-time quantitative PCR (qPCR) and high performance liquid chromatography (HPLC)-based technologies have also showed a broad application prospects in the bioanalysis of therapeutic oligonucleotides. However, each technology has its own advantages and limitations. This review summarizes the currently used techniques in the bioanalysis of oligonucleotide therapeutics and reviews the challenges of regulated bioanalysis.
Key words:    therapeutic oligonucleotides    bioanalysis    gene therapy    pharmacokinetics   
收稿日期: 2021-04-30
DOI: 10.16438/j.0513-4870.2021-0671
基金项目: 国家自然科学基金资助项目(U1603104,81874309,81803704).
通讯作者: 姜宏梁,E-mail:jianghongliang@hust.edu.cn
Email: jianghongliang@hust.edu.cn
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