演讲嘉宾

周德敏


北京大学药学院,天然药物及仿生药物国家重点实验室

会议报告摘要:基于基因密码子扩展和编辑的生物药物修饰新方法

人体细胞是生物药物的天然载体,其近三万个组成基因及产物成为生物药物的最重要来源。但是内源性物质绝大多数不能直接成药,需要进行结构修饰以提高它们的成药性。“基于基因密码子扩展和编辑的蛋白质标记”是报告人实验室发起的研究生物药物的新方法,该方法的核心是在蛋白质翻译过程中,利用终止密码子UAG作为新的编码子,将自然界中不存在的、但能人工合成的具有特殊性质的“人造氨基酸”,定点引入蛋白质的特定位点,实现在体蛋白质的非天然氨基酸定点标记。进而借助于该引入“人造氨基酸”的生物正交反应性质,实现蛋白质温和、快速、高效、定量和特异的定点修饰,特别是将具有特殊物理、化学和生物学性质的基团和功能分子选择性修饰内源性物质实现其功能调控,使内源性物质经过该化学修饰发挥其最佳生理功能,克服内源性物质在生物治疗和成药性方面存在的缺陷,取得对生物治疗具有重大推动作用的仿生技术突破。针对恶性肿瘤、自身免疫、遗传性疾病和急性传染病等重大疾病,推动包括基因治疗、免疫治疗、靶向治疗等生物技术药物研究的飞速发展。

研究方向

基于化学-生物学交叉的新药发现和药物创新的新技术新方法

     

生物360精选了周德敏教授在2016年发表的3篇文章,翻译摘要以供读者更好的了解其工作成果,详情访问

研究经历

1985–1990 北京医科大学,大学本科
1990–1996 北京医科大学/日本筑波大学,联合培养博士
1996–1998 日本筑波大学应用生物化学系,助理教授
1999–2002 美国加州大学伯克利分校化学系/Scripps研究所博士后
2002–2003 美国Chugai-Roche 制药公司,高级研究员
2003–2008 美国Immusol生物制药公司,创新药物研发部责任人
2008–今 北京大学药学院,教授、院长
           天然药物及仿生药物国家重点实验室主任


近期发表论文

  1. Ling Wu, Jingxian Chen, Yiming Wu, Bo Zhang, Xiaochun Cai, Ziwei Zhang, Yan Wang, LongLong Si, Huan Xu, YongXiang Zheng, ChuanLing Zhang, Chenggang Liang, Jing Li, Lihe Zhang, Qiang Zhang, Demin Zhou*Precise and combinatorial PEGylation generates a low-immunogenic, stable form of human growth hormone. J Control. Release, 2017, 249:84-93.
  2. Longlong Si, Huan Xu, Xueying Zhou, Ziwei Zhang, Zhenyu Tian, Yan Wang, Yiming Wu, Bo Zhang, Zhenlan Niu, Chuanling Zhang, Ge Fu, Sulong Xiao, Qing Xia, Lihe Zhang, Demin Zhou*. Generation of Influenza A Viruses as Live but Replication-incompetent Virus Vaccines. Science, 2016, 354(6316):1170-1173.
  3. Sulong Xiao, Longlong Si, Zhenyu Tian, Pingxuan Jiao, Zibo Fan, Kun Meng, Xiaoshu Zhou, Han Wang, Renyang Xu, Xu Han, Ge Fu, Yongmin Zhang, Lihe Zhang, Demin Zhou* Pentacyclic triterpenes grafted on CD cores to interfere with influenza virus entry: A dramatic multivalent effect. Biomaterials, 2016, 78, 74-85.
  4. Chuanling Zhang, Tianzhuo Yao, Yongxiang Zheng, Zhongjun Li, Qiang Zhang, Lihe Zhang and Demin Zhou*, Development of Next Generation of Adeno-Associated Viral Vectors via Precision Engineering for Preferable Selective Tropism and Efficient Gene Delivery. Biomaterials, 2016, 80, 134-145.
  5. Bo Zhang, Qi Yang, Jingxian Chen, Ling Wu, Tianzhuo Yao, Yiming Wu, Huan Xu, Lihe Zhang, Qing Xia*, Demin Zhou* CRISPRi-Manipulation of Genetic Code Expansion via RF1 for Reassignment of Amber Codon in Bacteria. Sci. Rep., 2016, 6, doi: 10.1038/srep20000.
  6. Bo Zhang, Huan Xu, Jingxian Chen, Yongxiang Zheng, Yiming Wu, Longlong Si, Ling Wu, Chuanling Zhang, Gang Xia, Lihe Zhang, and Demin Zhou* Development of next generation of therapeutic IFN-alpha2b via genetic code expansion. Acta Biomaterialia. 2015, 9: 100-111.
  7. Yongxiang Zheng, Fei Yu, Yiming Wu, Longlong Si, Huan Xu, Chuanling Zhang, Qing Xia, Sulong Xiao, Qi Wang, Qiuchen He, Peng Chen, Jiangyun Wang, Lihe Zhang, Kazunari Taira, Demin Zhou* Broaden the versatility of lentiviral vector as a tool in nucleic acid research via genetic code expansion. Nucleic Acids Res., 2015, 43(11):e73.
  8. Maorong Yu, Longlong Si, Yufei Wang, Yiming Wu, Fei Yu, Pingxuan Jiao, Yongying Shi, Han Wang, Sulong Xiao, Ge Fu, Ke Tian, Yitao Wang, Zhihong Guo, Xinshan Ye, Lihe Zhang and Demin Zhou* Discovery of Pentacyclic Triterpenoids as Potential Entry Inhibitors of Influenza Viruses. J. Med. Chem. 2014, 2014, 57(23): 10058-10071.
  9. Fei Yu, Qi Wang, Zhen Zhang, Yiyun Peng, Yunyan Qiu, Yongying Shi, Yongxiang Zheng, Sulong Xiao, Han Wang, Xiaoxi Huang, Linyi Zhu, Kunbo Chen, Chuanke Zhao, Chuanling Zhang, Maorong Yu, Dian Sun, Lihe Zhang, Demin Zhou* Development of oleanane-type triterpene as a new class of HCV entry inhibitors. J. Med. Chem. 2013, 56(11): 4300-4319.
  10. Xin Jin, Tingting Sun, Chuanke Zhao, Yongxiang Zheng, Yufan Zhang, Weijing Cai, Qiuchen He, Kaz Taira, Lihe Zhang, Demin Zhou* Strand antagonism in RNAi: An explanation of potency variation of dsRNA versus shRNA generated intracellularly, Nucleic Acid Res., 2012, 40, 1797-1806