长效干扰素研究进展

中国生物工程杂志

2010, Vol. 30

Issue (05): 122-127

综述

长效干扰素研究进展

田硕¹,徐晨^2*,姚文兵¹

1.中国药科大学南京 210009
2.北京三元基因工程有限公司北京 102600

The Advance in Long Effect Interferon Reserch

TIAN Shuo¹,XU Chen²,YAO Wen-bing¹

1.School of Science & Technology，China Pharmaceutical University, Nanjing 210009，China
2.Beijing TriPrime Genetic Engineering Co．Ltd．,Beijing102600，China

全文: PDF(497 KB) HTML

摘要：

干扰素是一类多功能细胞因子，是由哺乳动物细胞受到适宜刺激产生的一种微量的、具高度生物学活性的蛋白质，具有抵抗病毒感染、抑制肿瘤生长和调节机体免疫功能的作用。干扰素α血浆半衰期短而丙型和乙型肝炎治疗周期长，影响了患者的依从性。目前延长蛋白药物半衰期的方法主要有化学修饰、蛋白融合、定点突变技术联合和改造药物制剂释放系统，随着又一新型长效干扰素ZALBIN即将上市，长效干扰素再次成为医药行业的聚焦点。现针对干扰素α长效制剂中的最新研究进展进行综述。

关键词： 干扰素α; 半衰期; 定点突变; PEG化; 白蛋白融合

Abstract:

Interferons are a class of cytokines that play key roles in the regulation of cell growth and differentiation via activation of a cascade of intracellular pathways and represented the functions of antiviral, immunomodulatory, and antiproliferative effects，which are synthesized and secreted by somatic cells of all mammalian species. Interferon alpha (IFN-α) are used in clinic to treat a variety of viral diseases and cancers. Howerver，the short circulating half-life of IFN-α necessitates frequent administration to patients which limits the broader usage. The methods of prolonging the half-life of protein drug in common use are chemical modification, albumin fusion technology, analog construction and combination with drug delivery system. Herein the method of prolonging the half-life of IFN-α in the above-mentioned of the latest research methods were reviewed.

Key words: IFN-&alpha half-life Site-directed mutagenesis PEGylation Albumin fusion

收稿日期: 2010-01-29 出版日期: 2010-05-25

通讯作者: 徐晨 E-mail: xuchen@triprime.com

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	田硕
	徐晨
	姚文兵

引用本文:

田硕徐晨姚文兵. 长效干扰素研究进展[J]. 中国生物工程杂志, 2010, 30(05): 122-127.

TIAN Shuo, XU Chen, TAO Wen-Bing. The Advance in Long Effect Interferon Reserch. China Biotechnology, 2010, 30(05): 122-127.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2010/V30/I05/122

［1］ Roberts M J,Bentley M D,Harris J M. Chemistry for peptide and protein PEGylation.Adv Drug Deliv Rev,2002,54(4):459476.
［2］ Wang Y S,Yongster S,Grace M,et al. Structural and biological characterization of pegylated recombinant interferon alpha2b and its therapeutic applications.Adv Drug Deliv Rev, 2002, 54(4):547570.
［3］ Reddy K R, Modi M W, Pedder S. Use of peginterferon alfa2a (40KD) (Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev, 2002,54,571584.
［4］ Harris J M, Martin N E, Modi M. Pegylationa novel process for modifying pharmacokinetics. Clin Pharmacokinet,2001,40(7):539551.
［5］ Ramon J, Saez V, Baez R, et al. PEGylated interferonalpha2b: a branched 40K polyethylene glycol derivative. Pharm Res,2005, 22(8):13741386.
［6］ Jo Y W, Youn Y S, Lee S H, et al. Longacting interferonalpha2a modified with a trimerstructured polyethylene glycol: preparation, in vitro bioactivity, in vivo stability and pharmacokinetics. Int J Pharm, 2006, 309(12):8793.
［7］ Bell S J, Fam C M, Chlipala E A, et al. Enhance Circulating HalfLife and Antitumor Actiity of a SiteSpecific Pegylated Interferonα Protein Therapeutic. Bioconjugate Chem, 2008,19(1):299305.
［8］ Balan S, Choi J W, Godwin A, et al. SiteSpecific PEGylation of Protein Disulfide Bonds Using a ThreeCarbon Bridge. Bioconjugate Chem, 2007,18(1):6176.
［9］牛晓霞，刘金毅，杨轶，等. 集成干扰素突变体Ⅱ的分子构建、表达及提纯. 中国生物工程杂志, 2006,26(12):15. Niu X X , Liu J Y , Yang Y . Chin Biotechnol,2006,26(12):15.
［10］牛晓霞，周敏毅，刘金毅，等. 聚乙二醇定点修饰集成干扰素突变体Ⅱ.中国生物工程杂志,2008,28(4):1720. Niu X X , Zhou M Y, Liu J Y,et al . Chin Biotechnol, 2008,28(4):1720.
［11］ Bain V G,Kaita K D,Yoshida E M. A phase 2 study to evaluate the antiviral activity, safety,and pharmacokinetics of recombinant human albumininterferon alfa fusion protein in genotype 1 chronic hepatitis C. patients. J Hepatol,2006, 44(4):671678.
［12］ Zhao H L, Xue C, Wang Y, et al. Circumventing the heterogeneity and instability of human serum albumininterferonalpha2b fusion protein by altering its orientation. J Biotechnol. 2007,131(3):245252.
［13］ Zhao H L, Xue Q Y, Xue C, et al. Increasing the homogeneity, stability and activity of human serum albumin and interferonα2b fusion protein by linker engineering. Protein Express Purif ,2008, 61(1):7377.
［14］王磊，何剑，肖卫华. 毕赤酵母表达人干扰素α 2b和人IgG免疫球蛋白Fc片段融合蛋白显著延长体内半衰期. 生物工程学报, 2008, 24(1):5362. Wang L, He J, Xiao W H. Chin J Biotechnol, 2008, 24(1):5362.
［15］ Jones T D, Hanlon M, Smith B J, et al. The development of a modified human IFNalpha2b linked to the Fc portion of human IgG 1 as a novel potential therapeutic for the treatment of hepatitis C virus infection. J. Interferon Cytokine Res, 2004, 24(9): 560572.
［16］ Ceaglio N, Etcheverrigaray M, Kratje R, et al. Novel longlasting interferon alpha derivatives designed by glycoengineering. Biochimie,2008,90 (3):437449.
［17］ Drittanti L, Borrelly G, Guyon T, et al. Belerofon:a longlasting and orally available singleamino acid mutant of interferon alpha. J Interferon Cytokine Res , 2007,27:7091709.
［18］ De Leede L G, Humphries J E, Bechet A C, et al.Novel ControlledRelease LemnaDerived IFNalpha2b (Locteron):Pharmacokinetics, Pharmacodynamics, and Tolerability in a Phase I Clinical Trial. J Interferon Cytokine Res , 2008,28(2):113122.
［19］ Chan Y P, Meyrueix R, Kravtzoff R et al. Review on Medusa:a polymerbased sustained release technology for protein and peptide drugs. Expert Opin Drug Deliv , 2007, 4(4):441451.
［20］ Zhang Y M, Yang F, Yang Y Q, et al. Recombinant interferonalpha2b poly(lacticcoglycolic acid) microspheres: pharmacokineticspharmacodynamics study in rhesus monkeys following intramuscular administration. Acta Pharmacol Sin,2008,29(11):13701375.
［21］ Vyas S P, Rawat M, Rawat A, et al. Pegylated protein encapsulated multivesicular liposomes: a novel approach for sustained release of interferon alpha. Drug Dev Ind Pharm, 2006, 32(6):699707.
［22］ Ito Y, Saeki A, Shiroyama K, et al. Percutaneous absorption of interferonα by selfdissolving micropiles. J Drug Target, 2008,16(3):243249.

[1]	郭芳,张良,冯旭东,李春. 植物源UDP-糖基转移酶及其分子改造^*[J]. 中国生物工程杂志, 2021, 41(9): 78-91.
[2]	彭向雷,王烨,王丽男,苏彦斌,付远辉,郑妍鹏,何金生. 单引物PCR法引入定点突变 ^*[J]. 中国生物工程杂志, 2020, 40(8): 19-23.
[3]	赵晓艳,陈允妲,章雅倩,吴晓玉,王飞,陈金印. **Myxococcus sp.V11海藻糖合酶TreS II分子改造 ^***[J]. 中国生物工程杂志, 2020, 40(3): 79-87.
[4]	苏永君,胡蝶,胡博淳,李闯,文正,章晨,邬敏辰. 定点突变提高环氧化物水解酶AuEH2催化对甲基苯基缩水甘油醚的对映选择性^*[J]. 中国生物工程杂志, 2020, 40(3): 88-95.
[5]	阚婷婷,宗迅成,苏永君,王婷婷,李闯,胡蝶,邬敏辰. 定点突变改善PvEH1对邻甲基苯基缩水甘油醚的催化特性 ^*[J]. 中国生物工程杂志, 2019, 39(6): 9-16.
[6]	徐欢,周美玲,葛琳,王志明. 人血清白蛋白在蛋白多肽类药物长效化中的应用 ^*[J]. 中国生物工程杂志, 2019, 39(1): 82-89.
[7]	孟浩毅,李丹阳,孙正阳,杨兆勇,张志斐,袁丽杰. 人类线粒体肌酸激酶uMtCK的底物结合位点分析 ^*[J]. 中国生物工程杂志, 2018, 38(5): 24-32.
[8]	陈静, 康赐明, 罗文新. 治疗性抗体半衰期改造研究进展[J]. 中国生物工程杂志, 2017, 37(5): 87-96.
[9]	李雪晴, 袁风娇, 程建青, 董运海, 李剑芳, 邬敏辰. 杂合β-甘露聚糖酶AuMan5A^loop的H321对其酶学性质的影响[J]. 中国生物工程杂志, 2017, 37(2): 48-53.
[10]	李成媛, 张晶晶, 钱凯, 缪亚娜, 蔡燕飞, 杨剑峰, 何杨, 金坚. 人血清白蛋白-干扰素α2b融合蛋白在CHO细胞中的表达[J]. 中国生物工程杂志, 2016, 36(7): 7-14.
[11]	吴芹, 胡蝶, 李雪晴, 袁风娇, 李剑芳, 邬敏辰. Y13F定点突变改良米曲霉中温木聚糖酶的耐热性[J]. 中国生物工程杂志, 2016, 36(12): 36-41.
[12]	代玉环, 徐尧, 罗颖, 代洋, 石伟林, 徐瑶. Myocardin调控心肌H9C2细胞Ca²⁺通道机制研究[J]. 中国生物工程杂志, 2016, 36(11): 1-6.
[13]	向缅, 朱建全, 俞继华, 李洋洋, 李娟娟, 刘祖碧, 王万军, 廖海, 周嘉裕. 决明胰蛋白酶抑制剂1活性相关残基的定点突变与抑制活性分析[J]. 中国生物工程杂志, 2016, 36(10): 15-20.
[14]	李瑶瑶, 毕静, 王艺红, 秦云贺, 张雪莲. 乙酰化修饰调控结核杆菌异柠檬酸裂合酶的研究[J]. 中国生物工程杂志, 2015, 35(6): 8-13.
[15]	高瑞平, 程隆斌, 李振秋. 一种简便快速的单引物PCR定点突变方法[J]. 中国生物工程杂志, 2015, 35(5): 61-65.

Viewed

Full text

Abstract

Cited

Shared

Discussed