表观遗传药物研发的现状与挑战

Current Status and Challenges of Epigenetic Drug Research and Development

表观遗传修饰不影响DNA序列,却可通过DNA甲基化/去甲基化、多种类型组蛋白可逆修饰以及非编码RNA分子影响染色质活性状态,影响DNA遗传信息的表达。基于表观遗传机制的药物旨在通过人为干预疾病状态下染色质表观遗传修饰状态,以矫正疾病关联基因的表达,实现疾病预防和治疗。围绕DNA甲基转移酶抑制剂、组蛋白修饰酶抑制剂和siRNA等在内的表观遗传药物的研发现状进行了系统的总结,并对相关研发和产业化过程中所遇到的问题进行了系统的梳理和较为深入的讨论,旨为促进国内表观遗传药物的研发和相关生物技术产业化发展。

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.