Current Status and Challenges of Epigenetic Drug Research and Development

doi:10.13560/j.cnki.biotech.bull.1985.2019-0099

Abstract

Abstract: Epigenetic modifications do not affect DNA sequence,but do affect the expression of DNA genetic information by affecting the chromatin activity through DNA methylation/demethylation,reversible modifications of various histones,non-coding RNA molecules etc. Clinical drugs based on epigenetic mechanisms are intended to correct the expressions of the disease-associated genes by artificially interfering with the epigenetic modifications of the chromatins in the disease conditions,so as to achieve the preventions and treatments of diseases. To promote the research and development（R&D）of epigenetic drugs and its biotechnological industrialization in China,this paper systematically summarized the R&D current status of the epigenetic drugs,including DNA methyltransferase inhibitors,histone modifying enzyme inhibitors,siRNA,etc.,and also deeply discussed the critical issues that may need to be resolved in R&D and industrialization of epigenetic drugs.

Key words: epigenetic drug, DNA methylation inhibitor, histone modification inhibitor, siRNA

JIANG Rui, LÜ Ke-nao, PAN Xue-feng, CUI Xin-xia, SHEN Shi-gang, DING Liang. Current Status and Challenges of Epigenetic Drug Research and Development[J]. Biotechnology Bulletin, 2019, 35(8): 213-225.

References

[1] 韦平, 秦爱建. 重要动物病毒分子生物学[M]. 北京:科学出版社, 2008.
[2] 王小波, 周金柱, 俞天奇, 等. 猪皮炎肾病综合征的病理学观察[J]. 中国兽医学报, 2016(1):162-165.
[3] 王小波, 王海燕, 高杏, 等. 家养野猪自然感染猪圆环病毒2型的病理学观察[J]. 中国兽医学报, 2014, 34(8):1314-1318.
[4] Palinski R, Piñeyro P, Shang P, et al.A novel porcine circovirus distantly related to known circoviruses is associated with porcine dermatitis and nephropathy syndrome and reproductive failure[J]. J Virol, 2016, 91(1):1-13.
[5] Ou YT, Zhang XW, Liu XH, et al.Co-infection of swine with porcine circovirus type 2 and other swine viruses[J]. Viruses, 2019, 11(185):1-14.
[6] Huang Z, Su S, Wei CY, et al.Complete genome sequence of a novel field strain of rearranged porcine circovirus type 2 in southern China[J]. J Virol, 2012, 86(19):10895-10895.
[7] Hua T, Wang X, Bai J, et al.Attenuation of porcine circovirus type-2b by replacement with the Rep gene of porcine circovirus type-1[J]. Virus Res, 2013, 173(2):270-279.
[8] Karuppannan AK, Kwang J .ORF3 of porcine circovirus 2 enhances the in vitro and in vivo spread of the of the virus[J]. Virology, 2011, 410(1):248-256.
[9] Nawagitgul P, Morozov I, Bolin SR, et al.Open reading frame 2 of porcine circovirus type 2 encodes a major capsid protein[J]. J Gen Virol, 2000, 81(9):2281-2287.
[10] Santos MR, Assao VS, Santos FAA, et al.Utilization of phage display to identify antigenic regions in the PCV2 capsid protein for the evaluation of serological responses in mice and pigs[J]. Arch Virol, 2018, 163(7):1877-1887.
[11] 赵晓云, 乔绪稳, 陈瑾, 等. 利用E. coli表达猪圆环病毒2型Cap蛋白生产病毒样颗粒疫苗[J]. 中国农业科学, 2015, 48(5):976-986.
[12] 吴洋, 李庆伟, 杨娜娜. 猪PCV2 ORF2蛋白I-ELISA检测方法的建立及猪场血清抗体检测分析[J]. 免疫学杂志, 2015(1):71-73.
[13] 欧云文, 马小元, 王俊, 等. 猪圆环病毒2型ORF2基因的原核表达及反应原性分析[J]. 动物医学进展, 2017, 38(4):1-6.
[14] 张遥遥, 张小莺, 李新平. 猪圆环病毒2型Cap基因的原核表达及IgY多抗的制备[J]. 中国兽医科学, 2017, 47(6):727-732.
[15] 张蕾, 代松宝, 张丽琳, 等. PCV2逃逸宿主天然免疫的分子机制研究[J]. 华北农学报, 2018, 33(2):149-156.
[16] 徐文娟, 张瑛杰, 李青青, 等. 利用细菌展示技术系统地筛选猪圆环病毒2型衣壳蛋白的线性抗原区域[J]. 中国预防兽医学报, 2016, 38(5):398-402.
[17] 张晓, 尹秀凤, 徐凯, 等. 猪圆环病毒2型Cap蛋白在杆状系统中的表达与纯化[J]. 中国动物传染病学报, 2015(4):53-56.
[18] 陈灵艳, 陈先进, 蒋烨, 等. 猪圆环病毒衣壳蛋白在枯草芽孢杆菌中的表达研究[J]. 生物技术通报, 2016, 32(5):140-145.