研究方向为蛋白质折叠与修饰工程，以及重要疾病治疗的生物技术药物研发。主要方向为：（1）建立和发展新型高效的蛋白体外折叠复性及病毒样颗粒胞外自组装技术；（2）发展定点可控以及可逆的蛋白药物聚乙二醇修饰技术；（3）靶向和长效的蛋白纳米颗粒药物递送及多肽药物偶联技术；（4）建立生物技术新药的研制平台技术及过程控制。已完成十余种重组蛋白的制备工艺开发，作为主要技术负责人之一完成长效粒细胞集落刺激因子药物研发，并获得临床研究批件。

2017年可招收学术型及专业型硕士。

081703-生物化工

生物大分子纯化与修饰； 蛋白纳米颗粒药物递送； 抗体/多肽—药物偶联

2001-09--2007-06   中国科学院过程工程研究所   博士学位
1995-09--1998-06   北京化工大学   硕士学位
1988-09--1992-06   成都科技大学   学士学位

   

2016-08~现在, 中国科学院过程工程研究所, 研究员
2010-09~2011-09,美国华盛顿大学, 访问学者
2008-07~2016-07,中国科学院过程工程研究所, 副研究员
1998-06~2008-07,中国科学院过程工程研究所, 助理研究员

   

（ 1 ） 一种复合干扰素的纯化方法, 发明, 2006, 第 1 作者, 专利号: ZL 200310121343.5
（ 2 ） 聚乙二醇-葡激酶偶联物及其准备方法和应用, 发明, 2010, 第 4 作者, 专利号: ZL 201010514551.1
（ 3 ） 有机溶剂辅助PEG修饰蛋白质药物, 发明, 2010, 第 4 作者, 专利号: ZL 201010227151.2
（ 4 ） 重组人干扰素β-1b 的高压复性和组合层析制备方法, 发明, 2014, 第 1 作者, 专利号: 201410437913.X
（ 5 ） 一种以铁蛋白为载体的抗肿瘤药物及其制备方法, 发明, 2016, 第 1 作者, 专利号: 201610543500.9
（ 6 ） 一种含有邻苯二醌类官能团的聚乙二醇修饰剂及其制备方法和用途, 发明, 2016, 第 1 作者, 专利号: 201610616651.2
（ 7 ） 一种抗凝溶栓双功能融合蛋白的亲和复性及纯化方法, 发明, 2010, 第 5 作者, 专利号: ZL 201010279445.X
（ 8 ） 一种长效重组睫状神经营养因子及其制备方法和用途, 发明, 2017, 第 1 作者, 专利号: 201710184644.4
（ 9 ） 一种肿瘤靶向多肽-药物偶联衍生物、其制备方法及应用, 发明, 2016, 第 1 作者, 专利号: 201610899293.0
（ 10 ） 一种纳米载体蛋白及其制备方法和应用, 发明, 2017, 第 1 作者, 专利号: 201710875115.9
（ 11 ） 一种提高离子交换层析内毒素去除效率的方法及其用途, 发明, 2017, 第 1 作者, 专利号: 201710859565.9
（ 12 ） 一种重组病毒样颗粒及其制备方法和用途, 发明, 2019, 第 1 作者, 专利号: 201910013184.8
（ 13 ） 一种基于包涵体形式表达的重组病毒样颗粒及其制备方法和应用, 发明, 2019, 第 1 作者, 专利号: 201910406257.X

   

[1] 刘永东. A critical review of ferritin as a drug nanocarrier: structure, properties, comparative advantages and challenges.. PARTICUOLOGY. 2021, 
[2] Yin, Shuang, Wang, Yan, Zhang, Bingyang, Qu, Yiran, Liu, Yongdong, Dai, Sheng, Zhang, Yao, Wang, Yingli, Bi, Jingxiu. Engineered Human Heavy-Chain Ferritin with Half-Life Extension and Tumor Targeting by PAS and RGDK Peptide Functionalization. PHARMACEUTICS[J]. 2021, 13(4): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070472/.

[3] 刘永东. 多肽与化疗药物偶联提高药物的有效性和安全物. 过程工程学报. 2021, 
[4] Zhang, Yao, Liu, Yongdong, Zhang, Bingyang, Yin, Shuang, Li, Xiunan, Zhao, Dawei, Wang, Weiying, Bi, Jingxiu, Su, Zhiguo. In vitro preparation of uniform and nucleic acid free hepatitis B core particles through an optimized disassembly-purification-reassembly process. PROTEIN EXPRESSION AND PURIFICATION[J]. 2021, 178: http://dx.doi.org/10.1016/j.pep.2020.105747.

[5] Qi Wang, Chun Zhang, Zenglan Li, Fangxia Guo, Jing Zhang, Yongdong Liu, Zhiguo Su. High hydrostatic pressure refolding of highly hydrophobic protein: A case study of recombinant human interferon β-1b from inclusion bodies. Biochemical Engineering Journal. 2021, 172: http://dx.doi.org/10.1016/j.bej.2021.108055.

[6] Yin, Shuang, Zhang, Bingyang, Lin, Jianying, Liu, Yongdong, Su, Zhiguo, Bi, Jingxiu. Development of purification process for dual-function recombinant human heavy-chain ferritin by the investigation of genetic modification impact on conformation. ENGINEERING IN LIFE SCIENCES[J]. 2021, 21(10): 630-642, http://apps.webofknowledge.com/CitedFullRecord.do?product=UA&colName=WOS&SID=5CCFccWmJJRAuMzNPjj&search_mode=CitedFullRecord&isickref=WOS:000663354600001.

[7] Zhang, Yao, Yin, Shuang, Zhang, Bingyang, Bi, Jingxiu, Liu, Yongdong, Su, Zhiguo. HBc-based virus-like particle assembly from inclusion bodies using 2-methyl-2, 4-pentanediol. PROCESS BIOCHEMISTRY[J]. 2020, 89: 233-237, http://dx.doi.org/10.1016/j.procbio.2019.10.031.

[8] Liu, Jiangning, Zhao, Binbin, Xue, Ling, Wu, Jing, Xu, Yanfeng, Liu, Yongdong, Qin, Chuan. Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections. VIROLOGY JOURNAL[J]. 2020, 17(1): http://dx.doi.org/10.1186/s12985-020-01328-8.

[9] Zhang, Yao, Ma, Qunfeng, Wang, Junfeng, Ge, Jianlin, Hua, Jilei, Shi, Yinan, Zhang, Chi, Liu, Mengzhe, Wang, Yuqi, Chen, Zhinan, Wang, Ziling, Liu, Yongdong, Jiang, Hong. Expression, Purification, and Polyethylene Glycol Site-Specific Modification of Recombinant Human Interleukin 24 in Escherichia coli. PROTEIN JOURNAL[J]. 2019, 38(5): 576-585, 
[10] Wang, Chunyue, Zhang, Chun, Li, Zenglan, Yin, Shuang, Wang, Qi, Guo, Fangxia, Zhang, Yao, Yu, Rong, Liu, Yongdong, Su, Zhiguo. Extending Half Life of H-Ferritin Nanoparticle by Fusing Albumin Binding Domain for Doxorubicin Encapsulation. BIOMACROMOLECULES[J]. 2018, 19(3): 773-781, https://www.webofscience.com/wos/woscc/full-record/WOS:000427539600008.

[11] Guo, Fangxia, Liu, Yongdong, Zhang, Chun, Wang, Qi, Gao, Yuhui, Deng, Weiwei, Wang, Heng, Su, Zhiguo. Stabilization of a chimeric malaria antigen in separation and purification through efficient inhibition of protease activity by imidazole. PROCESS BIOCHEMISTRY[J]. 2018, 65: 213-219, http://dx.doi.org/10.1016/j.procbio.2017.10.013.

[12] Guo, Fangxia, Liu, Yongdong, Zhang, Chun, Wang, Qi, Wang, Lianyan, Gao, Yuhui, Bi, Jingxiu, Wang, Heng, Su, Zhiguo. Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin. BIOCONJUGATE CHEMISTRY[J]. 2018, 29(3): 761-770, http://www.irgrid.ac.cn/handle/1471x/1764212.

[13] Wang, Qi, Zhang, Chun, Liu, Liping, Li, Zenglan, Guo, Fangxia, Li, Xiunan, Luo, Jian, Zhao, Dawei, Liu, Yongdong, Su, Zhiguo. High hydrostatic pressure encapsulation of doxorubicin in ferritin nanocages with enhanced efficiency. JOURNAL OF BIOTECHNOLOGY[J]. 2017, 254: 34-42, http://dx.doi.org/10.1016/j.jbiotec.2017.05.025.

[14] Liu, Liping, Zhang, Chun, Li, Zenglan, Wang, Chunyue, Bi, Jingxiu, Yin, Shuang, Wang, Qi, Yu, Rong, Liu, Yongdong, Su, Zhiguo. Albumin Binding Domain Fusing R/K-X-X-R/K Sequence for Enhancing Tumor Delivery of Doxorubicin. MOLECULAR PHARMACEUTICS[J]. 2017, 14(11): 3739-3749, https://www.webofscience.com/wos/woscc/full-record/WOS:000414820000012.

[15] Zhang, Chun, Yu, Rong, Li, Zenglan, Feng, Cui, Wang, Qi, Liu, Yongdong, Su, Zhiguo. Development of long-acting ciliary neurotrophic factor by site-specific conjugation with different-sized polyethylene glycols and transferrin. INTERNATIONAL JOURNAL OF PHARMACEUTICS[J]. 2017, 529(1-2): 275-284, http://dx.doi.org/10.1016/j.ijpharm.2017.06.074.

[16] Xu, Longfu, Zhang, Chun, Liu, Liping, Zhang, Yao, Wang, Qi, Wang, Jian, Liu, Yongdong, Su, Zhiguo. Purification and characterization of a long-acting ciliary neurotrophic factor via genetically fused with an albumin-binding domain. PROTEIN EXPRESSION AND PURIFICATION[J]. 2017, 139: 14-20, http://dx.doi.org/10.1016/j.pep.2017.07.006.

[17] Xu, Longfu, Zhang, Chun, Wang, Qi, Guo, Fangxia, Li, Zenglan, Liu, Yongdong, Su, Zhiguo. Oxidized catechol-derived poly (ethylene glycol) for thiol-specific conjugation. REACTIVE & FUNCTIONAL POLYMERS[J]. 2017, 117: 97-105, http://dx.doi.org/10.1016/j.reactfunctpolym.2017.06.005.

[18] Wang, Qi, Zhang, Chun, Guo, Fangxia, Li, Zenglan, Liu, Yongdong, Su, Zhiguo. Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of Recombinant Human Ciliary Neurotrophic Factor. BIOCONJUGATE CHEMISTRY[J]. 2017, 28(11): 2841-2848, https://www.webofscience.com/wos/woscc/full-record/WOS:000415785600019.

[19] Yin Shuang, Zhang Chun, Li Zenglan, Wang Qi, Shi Hong, Yu Rong, Liu Yongdong, Su Zhiguo. Identification, characterization, and stabilization of the deamidation degradation of recombinant human tumor necrosis factor-α. Process Biochemistry[J]. 2017, 53: 216-223, http://dx.doi.org/10.1016/j.procbio.2016.11.011.

[20] Xue, Ling, Liu, Jiangning, Wang, Qi, Zhang, Chun, Xu, Longfu, Luo, Jian, Wang, Jian, Qin, Chuan, Liu, Yongdong, Su, Zhiguo. Purification and assembling a fused capsid protein as an enterovirus 71 vaccine candidate from inclusion bodies to pentamer-based nanoparticles. BIOCHEMICAL ENGINEERING JOURNAL[J]. 2017, 117: 139-146, http://dx.doi.org/10.1016/j.bej.2016.10.009.

[21] Wang, Qi, Liu, Yongdong, Zhang, Chun, Guo, Fangxia, Feng, Cui, Li, Xiunan, Shi, Hong, Su, Zhiguo. High hydrostatic pressure enables almost 100% refolding of recombinant human ciliary neurotrophic factor from inclusion bodies at high concentration. PROTEIN EXPRESSION AND PURIFICATION[J]. 2017, 133: 152-159, http://dx.doi.org/10.1016/j.pep.2017.03.014.

[22] Chen, Ying, Wang, Qi, Zhang, Chun, Li, Xiunan, Gao, Qiang, Dong, Changqing, Liu, Yongdong, Su, Zhiguo. Improving the refolding efficiency for proinsulin aspart inclusion body with optimized buffer compositions. PROTEIN EXPRESSION AND PURIFICATION[J]. 2016, 122(JUNE): 1-7, http://dx.doi.org/10.1016/j.pep.2016.01.015.

[23] 刘永东. 亲和纯化EV71融合多表位蛋白抗原及其自组装为病毒样蛋白颗粒. 中国生物工程杂志. 2016, 
[24] Li, Zenglan, Zhang, Yan, Wang, Qi, Li, Zhengjun, Liu, Yongdong, Zhang, Songping, Zhang, Guifeng, Ma, Guanghui, Luo, Jian, Su, Zhiguo. Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis. VACCINE[J]. 2016, 34(34): 4032-4039, http://dx.doi.org/10.1016/j.vaccine.2016.06.029.

[25] 殷爽, 冯翠, 张纯, 王祺, 王健, 余蓉, 刘永东, 苏志国. 转铁蛋白-PEG-睫状神经营养因子的制备及其生物活性评价. 中国生物工程杂志[J]. 2016, 36(4): "43-49", http://www.irgrid.ac.cn/handle/1471x/1188210.

[26] Zhao Dawei, Liu Yongdong, Zhang Guifeng, Zhang Chun, Li Xiunan, Wang Qingqing, Shi Hong, Su Zhiguo. Interaction of arginine with protein during refolding process probed by amide H/D exchange mass spectrometry and isothermal titration calorimetry.. Biochimica et biophysica acta. 2015, http://kns.cnki.net/KCMS/detail/detail.aspx?QueryID=0&CurRec=1&recid=&FileName=SJPD2BA2867147F796DE2D822EEB3FCF0FF6&DbName=SJPD_05&DbCode=SJPD&yx=&pr=&URLID=&bsm=.

[27] Zhang, Chun, Liu, Yongdong, Feng, Cui, Wang, Qi, Shi, Hong, Zhao, Dawei, Yu, Rong, Su, Zhiguo. Loss of PEG chain in routine SDS-PAGE analysis of PEG-maleimide modified protein. ELECTROPHORESIS[J]. 2015, 36(2): 371-374, http://www.irgrid.ac.cn/handle/1471x/945071.

[28] Zhang, Chun, Liu, Yongdong, Zhao, Dawei, Li, Xiunan, Yu, Rong, Su, Zhiguo. Facile purification of Escherichia coli expressed tag-free recombinant human tumor necrosis factor alpha from supernatant. PROTEIN EXPRESSION AND PURIFICATION[J]. 2014, 95(1): 195-203, http://dx.doi.org/10.1016/j.pep.2013.12.012.

[29] 刘永东. PEGylation of G-CSF in organic solvent markedly increases the efficacy and reactivity through protein unfolding, hydrolysis inhibition and solvent effect. Journal of Biotechnology. 2014, 
[30] Zhao, Dawei, Liu, Yongdong, Wang, Yinjue, Li, Xiunan, Wang, Qingqing, Su, Zhiguo. Membrane combined with hydrophilic macromolecules enhances protein refolding at high concentration. PROCESS BIOCHEMISTRY[J]. 2014, 49(7): 1129-1134, http://dx.doi.org/10.1016/j.procbio.2014.03.010.

[31] Zhao, Lan, Liu, Yongdong, Wang, Yinjue, Huang, Yongdong, Li, Xiunan, Li, Yan, Ma, Guanghui, Su, Zhiguo. Determination of leakage from antibody adsorbent: composition analysis and pH effect. BIOMEDICAL CHROMATOGRAPHY[J]. 2013, 27(9): 1089-1091, http://ir.ipe.ac.cn/handle/122111/13762.

[32] 刘永东. PEGylation of Protein in Organic Solution: a Case Study for Interferon beta-1b. Bioconjugate Chemistry. 2012, 
[33] Wang, Jun, Wang, Yinjue, Hu, Tao, Li, Xiunan, Huang, Yongdong, Liu, Yongdong, Ma, Guanghui, Su, Zhiguo. An oriented adsorption strategy for efficient solid phase PEGylation of recombinant staphylokinase by immobilized metal-ion affinity chromatography. PROCESS BIOCHEMISTRY[J]. 2012, 47(1): 106-112, http://dx.doi.org/10.1016/j.procbio.2011.10.016.

[34] Wang, Peng, Wang, Yunshan, Liu, Yongdong, Shi, Hong, Su, Zhiguo. Novel in situ product removal technique for simultaneous production of propionic acid and vitamin B12 by expanded bed adsorption bioreactor. BIORESOURCE TECHNOLOGY[J]. 2012, 104: 652-659, http://dx.doi.org/10.1016/j.biortech.2011.10.047.

[35] Zhao, Lan, Liu, Yongdong, Huang, Yongdong, Li, Xiunan, Wang, Yinjue, Li, Yan, Ma, Guanghui, Su, Zhiguo. Deliberate manipulation of the surface hydrophobicity of an adsorbent for an efficient purification of a giant molecule with multiple subunits. JOURNAL OF SEPARATION SCIENCE[J]. 2011, 34(22): 3186-3193, http://www.irgrid.ac.cn/handle/1471x/735896.

[36] Wang, Jun, Hu, Tao, Liu, Yongdong, Zhang, Guifeng, Ma, Guanghui, Su, Zhiguo. Kinetic and stoichiometric analysis of the modification process for N-terminal PEGylation of staphylokinase. ANALYTICAL BIOCHEMISTRY[J]. 2011, 412(1): 114-116, http://dx.doi.org/10.1016/j.ab.2010.12.030.

[37] 郝素娟, 汪音爵, 康爱君, 刘永东, 李秀男, 石红, 马润宇, 马光辉, 苏志国. 非糖基化促红细胞生成素的聚乙二醇定点修饰及修饰产物性质. 高等学校化学学报[J]. 2010, 2239-2245, http://lib.cqvip.com/Qikan/Article/Detail?id=36243741.

[38] Wang YinJue, Hao SuJuan, Liu YongDong, Hu Tao, Zhang GuiFeng, Zhang Xuan, Qi QingSheng, Ma GuangHui, Su ZhiGuo. PEGylation markedly enhances the in vivo potency of recombinant human non-glycosylated erythropoietin: a comparison with glycosylated erythropoietin.. Journal of controlled release : official journal of the Controlled Release Society. 2010, http://kns.cnki.net/KCMS/detail/detail.aspx?QueryID=0&CurRec=1&recid=&FileName=SJPD12102101074527&DbName=SJPD_01&DbCode=SJPD&yx=&pr=&URLID=&bsm=.

[39] 刘永东. Efficient preparation and PEGylation of recombinant human non-glycosylated erythropoietin expressed as inclusion body in E. coli.. International journal of pharmaceutics. 2009, 
[40] Wang, Fangwei, Liu, Yongdong, Ma, Guanghui, Su, Zhiguo. Glycerol-Assisted Hydrophobic Interaction Chromatography Improving Refolding of Recombinant Human Granulocyte Colony-Stimulating Factor. APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY[J]. 2009, 159(3): 634-641, http://www.irgrid.ac.cn/handle/1471x/736524.

[41] Chen, Jing, Liu, Yongdong, Li, Xiunan, Wang, Yinjue, Ding, Hong, Ma, Guanghui, Su, Zhiguo. Cooperative effects of urea and L-arginine on protein refolding. PROTEIN EXPRESSION AND PURIFICATION[J]. 2009, 66(1): 82-90, http://dx.doi.org/10.1016/j.pep.2009.02.004.

[42] Chen, Jing, Liu, Yongdong, Wang, Yinjue, Ding, Hong, Su, Zhiguo. Different Effects of L-Arginine on Protein Refolding: Suppressing Aggregates of Hydrophobic Interaction, Not Covalent Binding. BIOTECHNOLOGY PROGRESS[J]. 2008, 24(6): 1365-1372, http://www.irgrid.ac.cn/handle/1471x/725217.

[43] Liu, YongDong, Zhang, GuiFeng, Li, JingJing, Chen, Jing, Wang, YinJue, Ding, Hong, Su, ZhiGuo. Identification of an oxidative refolding intermediate of recombinant consensus interferon from inclusion bodies and design of a two-stage strategy to promote correct disulfide-bond formation. BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY[J]. 2007, 48: 189-198, http://www.irgrid.ac.cn/handle/1471x/725725.

[44] Liu, Yongdong, Li, Jingjing, Wang, Fangwei, Chen, Jing, Li, Peng, Su, Zhiguo. A newly proposed mechanism for arginine-assisted protein refolding - not inhibiting soluble oligomers although promoting a correct structure. PROTEIN EXPRESSION AND PURIFICATION[J]. 2007, 51(2): 235-242, http://dx.doi.org/10.1016/j.pep.2006.07.001.

[45] Fangwei Wang, Yongdong Liu, Jingjing Li, Guanghui Ma, Zhiguo Su. On-column refolding of consensus interferon at high concentration with guanidine-hydrochloride and polyethylene glycol gradients. Journal of Chromatography A. 2006, 1115(1): 72-80, http://dx.doi.org/10.1016/j.chroma.2006.02.075.

   

（ 1 ） 氢交换和液质联用研究助溶剂对蛋白动态折叠的影响, 主持, 国家级, 2010-01--2012-12
（ 2 ） PEG化粒细胞集落刺激因子的研究, 主持, 国家级, 2009-06--2010-12
（ 3 ） PEG修饰蛋白质药物技术及产业化, 主持, 国家级, 2009-03--2010-12
（ 4 ） 门冬胰岛素的高效复性, 主持, 国家级, 2014-01--2016-12
（ 5 ） 新型预防性疫苗品种及关键技术研发, 主持, 国家级, 2013-01--2015-12
（ 6 ） Development of protein continuous refolding and pu, 主持, 部委级, 2015-01--2016-12
（ 7 ） 病毒样蛋白颗粒疫苗胞外自组装机理及过程研究, 主持, 国家级, 2016-01--2019-12
（ 8 ） 融合蛋白中靶向肽RGD-4C定向成环及活性评价, 主持, 省级, 2016-01--2018-12
（ 9 ） 长效药物PG-30-N 关键生产工艺开发, 主持, 院级, 2013-01--2015-12
（ 10 ） 重组蛋白分离纯化工艺开发, 主持, 院级, 2015-06--2016-12
（ 11 ） 肠道病毒EV71型多表位融合抗原蛋白分离纯化, 参与, 研究所（学校）, 2014-06--2016-06
（ 12 ） PEG30-rhG-CSF注射液临床批件（中国科学院过程所部分）及技术转让, 主持, 研究所（学校）, 2016-02--2020-12
（ 13 ） EGF重组蛋白制备工艺开发, 主持, 院级, 2018-08--2019-12
（ 14 ） 亲和介质配体工艺开发, 主持, 院级, 2019-10--2021-12

与多家国内科研机构及企业合作。合作单位包括医科院、军科院、北京双鹭药业、北京甘李药业、北京生物制品所等

已指导学生

徐龙福  硕士研究生  081703-生物化工  

现指导学生

张耀  博士研究生  081703-生物化工  

刘雪  硕士研究生  085216-化学工程  

张宇翔  硕士研究生  085238-生物工程