我国核酸药物市场分析及对策建议

doi:10.13523/j.cb.2103061

中国生物工程杂志

2021, Vol. 41

Issue (7): 99-109 DOI: 10.13523/j.cb.2103061

行业分析

我国核酸药物市场分析及对策建议

刘少金(

),冯雪娇,王俊姝,肖正强,程平生

江西省科学院科技战略研究所南昌 330096

Market Analysis and Countermeasures of Nucleic Acid Drugs in China

LIU Shao-jin(

),FENG Xue-jiao,WANG Jun-shu,XIAO Zheng-qiang,CHENG Ping-sheng

Institute of Science and Technology Strategy, Jiangxi Academy of Sciences, Nanchang 330096,China

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摘要：

近年来,因兼具基因修饰和传统药物的双重特点,核酸药物已逐渐成为精准生物医学和疾病治疗的热点。为进一步推动我国核酸药物行业创新发展,采用定量分析和定性分析相结合的方法,对国内外核酸药物获批/授权、市场和研发情况进行分析,揭示全球ASO、siRNA、RNA aptamer及mRNA等四大类核酸药物的产业发展态势,系统梳理我国支持核酸药物创新发展的政策与措施,明确未来的技术主攻方向和应用潜力。面对国内基因治疗的迫切需求及核酸药物创制的严峻形势,研究提出推动源头创新、完善成果转移转化机制和营造良好竞争环境等对策建议。

关键词： 核酸药物; 反义寡核苷酸药物; siRNA药物; 核酸适配体药物; mRNA药物

Abstract:

In recent years, due to the dual characteristics of genetic modification and traditional drugs, nucleic acid drugs have gradually attracted tremendous attention in the field of precision biomedicine and disease treatment. In order to further promote the innovation and development of nucleic acid drug industry of China, a combination of quantitative analysis and qualitative analysis have been used to analyze the situation of nucleic acid drugs of approval/authorization, market and research domestically and abroad. The results showed the global R&D status and industry development trends of four major categories of nucleic acid drugs: ASO, siRNA, RNA aptamer and mRNA. Besides, policies and measures to support the innovation and development of nucleic acid drugs in China, and the main direction of future technology and application potential have been sorted out and analyzed. Facing the urgent domestic demand for gene therapy and the severe situation in the innovation of nucleic acid drugs, countermeasures and suggestions have been put forward to promote innovation at the source, improve the mechanism for transfer and transformation of results, and create a good competitive environment.

Key words: Nucleic acid drug ASO drugs siRNA drugs RNA aptamer drugs mRNA drugs

收稿日期: 2021-03-23 出版日期: 2021-08-03

ZTFLH:

Q819

通讯作者: 刘少金 E-mail: liusj9112@126.com

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引用本文:

刘少金,冯雪娇,王俊姝,肖正强,程平生. 我国核酸药物市场分析及对策建议[J]. 中国生物工程杂志, 2021, 41(7): 99-109.

LIU Shao-jin,FENG Xue-jiao,WANG Jun-shu,XIAO Zheng-qiang,CHENG Ping-sheng. Market Analysis and Countermeasures of Nucleic Acid Drugs in China. China Biotechnology, 2021, 41(7): 99-109.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2103061 或 https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I7/99

表1 全球核酸药物获批情况

表2 全球mRNA疫苗获授权情况

图1 2018~2024年全球核酸药物市场规模及预测

图2 2017~2020年Patisiran、Nusinersen和Eteplirsen全球市场规模及预测

表3 全球Aptamer药物临床试验数据(截至2020年12月)

表4 全球其他核酸药物临床试验数据(截至2020年12月)

表5 核酸药物在我国罕见病领域的市场规模预测

表6 我国核酸药物临床试验数据(截至2020年12月)

[1]	冯琦. 核酸药物的研究现状与展望. 中国生化药物杂志, 1997, 17(3):156-159.
	Feng Q. Progress and prospects of nucleic acid drugs. Chinese Journal of Biochemical Pharmaceutics, 1997, 17(3):156-159.
[2]	Opalinska J B, Gewirtz A M. Nucleic-acid therapeutics: basic principles and recent applications. Nature Reviews Drug Discovery, 2002, 1(7):503-514. pmid: 12120257
[3]	Cech T R, Steitz J A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 2014, 157(1):77-94. doi: 10.1016/j.cell.2014.03.008
[4]	Lächelt U, Wagner E. Nucleic acid therapeutics using polyplexes: a journey of 50 years (and beyond). Chemical Reviews, 2015, 115(19):11043-11078. doi: 10.1021/cr5006793 pmid: 25872804
[5]	王均, 王兰, 吕家臻, 等. 上市核酸药物的疗效分析和研究进展. 中国新药杂志, 2019, 28(18):2217-2224.
	Wang J, Wang L, Lv J Z, et al. Progress in efficacy analysis and development of listed nucleic acid drugs. Chinese Journal of New Drugs, 2019, 28(18):2217-2224.
[6]	Moreno P M D, Pêgo A P. Therapeutic antisense oligonucleotides against cancer: hurdling to the clinic. Frontiers in Chemistry, 2014, 2:87. doi: 10.3389/fchem.2014.00087 pmid: 25353019
[7]	Sundaram P, Kurniawan H, Byrne M E, et al. Therapeutic RNA aptamers in clinical trials. European Journal of Pharmaceutical Sciences, 2013, 48(1-2):259-271. doi: 10.1016/j.ejps.2012.10.014 pmid: 23142634
[8]	Digenio A, Dunbar R L, Alexander V J, et al. Antisense-mediated lowering of plasma apolipoprotein C-III by volanesorsen improves dyslipidemia and insulin sensitivity in type 2 diabetes. Diabetes Care, 2016, 39(8):1408-1415. doi: 10.2337/dc16-0126 pmid: 27271183
[9]	Wong E, Goldberg T. AMipomersen (kynamro): a novel antisense oligonucleotide inhibitor for the management of homozygous familial hypercholesterolemia. P & T: A Peer-Reviewed Journal for Formulary Management, 2014, 39(2):119-122.
[10]	Mendell J R, Goemans N, Lowes L P, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Annals of Neurology, 2016, 79(2):257-271. doi: 10.1002/ana.24555 pmid: 26573217
[11]	Stein C A, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Molecular Therapy, 2017, 25(5):1069-1075. doi: 10.1016/j.ymthe.2017.03.023
[12]	Benson M D, Waddington-Cruz M, Berk J L, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. The New England Journal of Medicine, 2018, 379(1):22-31. doi: 10.1056/NEJMoa1716793
[13]	Heo Y A. Golodirsen: first approval. Drugs, 2020, 80(3):329-333. doi: 10.1007/s40265-020-01267-2
[14]	Paik J, Duggan S. Volanesorsen: first global approval. Drugs, 2019, 79(12):1349-1354. doi: 10.1007/s40265-019-01168-z
[15]	Richardson P G, Riches M L, Kernan N A, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood, 2016, 127(13):1656-1665. doi: 10.1182/blood-2015-10-676924 pmid: 26825712
[16]	Adams D, O’Riordan A, Gonzalez-Duarte W D, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. The New England Journal of Medicine, 2018, 379(1):11-21. doi: 10.1056/NEJMoa1716153
[17]	Balwani M, Sardh E, Ventura P, et al. Phase 3 trial of RNAi therapeutic givosiran for acute intermittent Porphyria. The New England Journal of Medicine, 2020, 382(24):2289-2301. doi: 10.1056/NEJMoa1913147
[18]	Scott L J, Keam S J. Lumasiran: first approval. Drugs, 2021, 81(2):277-282. doi: 10.1007/s40265-020-01463-0
[19]	Raal F J, Kallend D, Ray K K, et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia. The New England Journal of Medicine, 2020, 382(16):1520-1530. doi: 10.1056/NEJMoa1913805
[20]	Polack F P, Thomas S J, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. The New England Journal of Medicine, 2020, 383(27):2603-2615. doi: 10.1056/NEJMoa2034577
[21]	Corbett K S, Flynn B, Foulds K E, et al. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. The New England Journal of Medicine, 2020, 383(16):1544-1555. doi: 10.1056/NEJMoa2024671
[22]	Wang F, Zuroske T, Watts J K. RNA therapeutics on the rise. Nature Reviews Drug Discovery, 2020, 19(7):441-442. doi: 10.1038/d41573-020-00078-0
[23]	杨若南, 许丽, 徐萍, 等. RNA疗法产业发展态势分析及建议. 中国生物工程杂志, 2021, 41(Z1):162-171.
	Yang R N, Xu L, Xu P, et al. The development situation and suggestions of RNA therapy industry. China Biotechnology, 2021, 41(Z1):162-171.
[24]	Bennett C F. Therapeutic antisense oligonucleotides are coming of age. Annual Review of Medicine, 2019, 70:307-321. doi: 10.1146/annurev-med-041217-010829 pmid: 30691367
[25]	Inoue H, Hayase Y, Imura A, et al. Synthesis and hybridization studies on two complementary nona (2'-O-methyl) ribonucleotides. Nucleic Acids Research, 1987, 15(15):6131-6148. pmid: 3627981
[26]	Fucini R V, Haringsma H J, Deng P, et al. Adenosine modification may be preferred for reducing siRNA immune stimulation. Nucleic Acid Therapeutics, 2012, 22(3):205-210. doi: 10.1089/nat.2011.0334
[27]	Summerton J, Weller D. Morpholino antisense oligomers: design, preparation, and properties. Antisense & Nucleic Acid Drug Development, 1997, 7(3):187-195.
[28]	Christensen U, Jacobsen N, Rajwanshi V K, et al. Stopped-flow kinetics of locked nucleic acid (LNA)-oligonucleotide duplex formation: studies of LNA-DNA and DNA-DNA interactions. Biochemical Journal, 2001, 354(3):481-484. doi: 10.1042/bj3540481
[29]	Karikó K, Muramatsu H, Welsh F A, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy, 2008, 16(11):1833-1840. doi: 10.1038/mt.2008.200
[30]	Kormann M S D, Hasenpusch G, Aneja M K, et al. Expression of therapeutic proteins after delivery of chemically modified mRNA in mice. Nature Biotechnology, 2011, 29(2):154-157. doi: 10.1038/nbt.1733
[31]	Jayaraman M, Ansell S M, Mui B L, et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angewandte Chemie (International Edition in English), 2012, 51(34):8529-8533.
[32]	Davis M E. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Molecular Pharmaceutics, 2009, 6(3):659-668. doi: 10.1021/mp900015y pmid: 19267452
[33]	Rozema D B, Lewis D L, Wakefield D H, et al. Dynamic polyconjugates for targeted in vivo delivery of siRNA to hepatocytes. PNAS, 2007, 104(32):12982-12987. pmid: 17652171
[34]	Khorev O, Stokmaier D, Schwardt O, et al. Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor. Bioorganic & Medicinal Chemistry, 2008, 16(9):5216-5231. doi: 10.1016/j.bmc.2008.03.017
[35]	Hu B, Zhong L P, Weng Y H, et al. Therapeutic siRNA: state of the art. Signal Transduction and Targeted Therapy, 2020, 5(1):1-25. doi: 10.1038/s41392-019-0089-y
[36]	Kranz L M, Diken M, Haas H, et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature, 2016, 534(7607):396-401. doi: 10.1038/nature18300
[37]	Rezaee M, Oskuee R K, Nassirli H, et al. Progress in the development of lipopolyplexes as efficient non-viral gene delivery systems. Journal of Controlled Release, 2016, 236:1-14. doi: 10.1016/j.jconrel.2016.06.023 pmid: 27317365
[38]	Weng Y H, Xiao H H, Zhang J C, et al. RNAi therapeutic and its innovative biotechnological evolution. Biotechnology Advances, 2019, 37(5):801-825. doi: 10.1016/j.biotechadv.2019.04.012
[39]	Ann Ran F, Hsu P D, Wright J, et al. Genome engineering using the CRISPR-Cas9 system. Nature Protocols, 2013, 8(11):2281-2308. doi: 10.1038/nprot.2013.143 pmid: 24157548
[40]	国家卫生健康委. 罕见病诊疗指南(2019年版).[2021-02-03]. http://www.nhc.gov.cn/yzygj/s7659/201902/61d06b4916c348e0810ce1fceb844333.shtml .
	National Health Commission of the People’s Republic of China. Guidelines for diagnosis and treatment of rare diseases (2019 Edition). [2021-02-03]. http://www.nhc.gov.cn/yzygj/s7659/201902/61d06b4916c348e0810ce1fceb844333.shtml .
[41]	谢雨礼. RNA药物的未来发展方向. 张江科技评论, 2020(3):50.
	Xie Y L. The future development of RNA drugs. Zhangjiang Technology Review, 2020(3):50.

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