王皓毅，博士，ac米兰中国官网器官再生与智造全国重点实验室研究员，基因工程技术研究组组长。长期从事新型基因编辑技术和细胞治疗技术开发工作，近年来开发多种新型TnpB小型基因编辑工具和DNA转座子工具，这些原创性技术的建立为解决基因编辑关键“卡脖子”技术对我国相关产业发展的限制提供了重要支撑。在人多能性干细胞和T细胞中建立了高效的基因编辑方法，开发了多种基因编辑构建增强型和通用型CAR-T细胞策略，并合作开展了基因编辑CAR-T细胞治疗实体肿瘤的临床研究，入选国家引才项目（2015年）。任中国遗传学会基因编辑分会副主任委员、国际人类可遗传基因编辑委员会委员。近年来承担国家重点研发计划并担任首席科学家，承担中科院先导专项子课题和农业农村部项目课题，承担国家自然科学基金优秀青年基金项目、面上项目，并获得国家杰出青年科学基金项目资助。相关研究成果发表在Cell、Nature Biotechnology、Cancer Cell、Cell Stem Cell、Cell Research、Nucleic Acid Research等杂志上，已发表SCI学术论文八十余篇，总引用次数过一万七千余次 (google scholar统计)。申请中国专利11项，授权3项；申请PCT专利5项，其中一项进入日本获得授权。

教育经历：

2003-2009  美国华盛顿大学  分子细胞生物学  博士

2001-2003  美国迈阿密大学  动物学          硕士

1997-2001  厦门大学        生物学          学士

高效和精确的基因工程技术对于生物医学的研究和应用具有极其重要的价值。研究组的科研兴趣在于开发和应用最新的基因工程技术，在人细胞中进行精确的基因修饰与改造。一方面挖掘开发全新的基因编辑与基因写入工具，建立全新基因组改造技术；另一方面应用这些技术在T细胞和干细胞中进行基因改造，建立新型细胞治疗方法；。研究组研究方向主要集中在以下两个方面:

一 新型基因编辑工具开发 

ZFN、TALEN和CRISPR技术乃至分子生物学中广泛运用的限制性内切酶和DNA聚合酶等工具酶大部分来自于不同物种的功能基因研究。随着基因组学的发展，大量新物种的基因组完成测序和组装，但大量编码新型蛋白的基因功能未知。我们希望基于数据驱动的研究模式，充分利用人工智能工具和高通量自动化实验平台，高效挖掘具有成为基因工程新工具潜力的候选系统，然后通过进一步优化，构建具有新功能特性的基因工程新技术，为生物学研究和疾病治疗提供更为有力的工具。

二 利用基因编辑技术开发新型细胞治疗技术

嵌合抗原受体修饰（chimeric antigen receptor，CAR）T 细胞疗法作为全新的肿瘤治疗方法在临床上凸显出广阔的应用前景。这些以T细胞为基础的疗法和基因编辑相结合具有重大的应用价值。因此我们在T细胞中优化基因编辑技术，建立新型的细胞治疗方法。同时我们也在T细胞中建立进行高通量遗传学和小分子筛选的技术，以期为免疫治疗发现新的治疗靶点和药物。

（*共同第一作者, ^#共同通讯作者）

1. Tang N*^#, Cheng L*, Hao J, Xu B, Pan X, Wei X, Wu H^#, Wang H^#, “Development of CAR‑T cell therapy for NF1/SWN‑related nerve sheath tumor treatment.” Acta Neuropathologica Communications, 2025; 13(1):45.
2. Zhang X*, Zhang C*, Lu S*, Dong J*, Tang N, Wang Y, Han W, Pan X, Zhang X, Liu D, Shyh-Chang N, Wang Y, Feng G, Wang H, “Miltefosine reinvigorates exhausted T cells by targeting their bioenergetic state.” Cell reports Medicine, 2024;5:101869
3. Hu X*, Zhang X*, Sun W*^#, Liu C*, Deng P, Cao Y, Zhang C, Xu N, Zhang T, Zhang Y, Liu J, Wang H^#，“Systematic discovery of DNA-binding tandem repeat proteins”. Nucleic Acids Research, 2024; 52(17), 10464–10489.
4. Zhang X*, Hu X*, Zhang T, Yang L, Liu C, Xu N, WangH^#, Sun W^#, “PLM_Sol: predicting protein solubility by benchmarking multiple protein language models with the updated Escherichia coli protein solubility dataset.” Briefings in Bioinformatics, 2024; 25(5), bbae404.
5. Zhang T*, Tan S*, Tang N*, Li Y* , Zhang C , Sun J , Guo Y, Gao H, Cai Y, Sun W, Wang C, Fu L, Ma H , Wu Y, Hu X, Zhang X, Gee P , Yan W , Zhao Y, Chen Q , Guo B , Wang H^#, Zhang Y#，“Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.” Cell, 2024; 187(14):3741-3760. e30.
6. Zhang X, Wang H, “Unlocking CAR T cell potential: Inosine-induced stemness and enhanced potency.” Cancer Cell, 2024; 42(2): 175-177.
7. Lin Q, Cao Y, Han G, Sun W, Weng W, Chen H#, Wang H^#, Kong J^#, “Programmable Clostridium perfringens Argonaute-Based, One-Pot Assay for the Multiplex Detection of miRNAs.” Analytical Chemistry, 2023; 95 (36): 13401-13406.
8. Xiang G^#*, Li Y*, Sun J*, Huo Y*, Cao S, Cao Y, Guo Y, Yang L, Cai Y, Zhang Y^#, Wang H^#,“Evolutionary mining and functional characterization of TnpB nucleases identify efficient miniature genome editors.” Nature Biotechnology, 2024; 42（5）: 745–757.
9. Deng P*, Tan S*, Yang Q, Fu L, Wu Y, Zhu H, Sun L, Bao Z, Lin Y, Zhang Q, Wang H, Wang J^#, Liu J^#,“Structural RNA components supervise the sequential DNA cleavage in R2 retrotransposon. ” Cell , 2023 Jun; 186 (13): 2865-2879. e20.
10. Wang Y*, Yang N*, Sun W*, Zhao C, Hu X, Lu S, Cao S, Wang N, Hai T, Feng G^#, An C^#, Wang H^#, “Characterisation of X chromosome status of human extended pluripotent stem cells.” Cell proliferation. 2023 Mar; Online.
11. Song Y*, Chen M*, Zhang Y, Li J, Liu B, Li N, Qiao M, Wang N, Cao Y, Lu S, Chen J, Sun W^#, Gao F^#, Wang H^#. “Loss of circSRY reduces γH2AX level in germ cells and impairs mouse spermatogenesis.” Life Science Alliance, 2022 Nov; ;6(2): e202201617. doi: 10.26508/lsa. 202201617. 
12. Zhang X*, Zhang C*, Qiao M*, Cheng C, Tang N, Lu S, Sun W, Xu B, Cao Y, Wei X, Wang Y, Han W, Wang H. “Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells.” Cancer Cell, 2022; 40(11):1407-1422.e7.
13. Li G*, Li X*, Zhuang S*, Wang L*, Zhu Y*, Chen Y*, Sun W*, Wu Z*, Zhou Z*, Chen J^#, Huang X#, Wang J#, Li D#, Li W#, Wang H^#, Wei W^#. “Gene editing and its applications in biomedicine.” Science China-Life Sciences, 2022 Apr; 65(4):660-700.
14. Wu T*, Cao Y*, Liu Q, Wu X, Shang Y, Piao J, Li Y, Dong Y, Liu D, Wang H ^#, Liu J^#, Ding B^#. “Genetically Encoded Double-Stranded DNA-Based Nanostructure Folded by a Covalently Bivalent CRISPR/dCas System.” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2022 Apr; 144(14):6575-6582.
15. Guo Y*, Xu B*, Wu Z*, Bo J#, Tong C, Chen D, Wang J, Wang H^#, Wang Y,^# Han W^#. “Mutant B2M-HLA-E and B2M-HLA-G fusion proteins protects universal chimeric antigen receptor-modified T cells from allogeneic NK cell-mediated lysis.” EUROPEAN JOURNAL OF IMMUNOLOGY, 2021; 51(10):2513-2521.
16. Wang Z*, Li N*, Feng K*, Chen M, Zhang Y, Liu Y, Yang Q, Nie J, Tang N, Zhang X, Cheng C, Shen L, He J, Ye X, Cao W^#, Wang H^#, Han W^#. “Phase I study of CAR-T cells with PD-1 and TCR disruption in mesothelin-positive solid tumors.” Cellular & Molecular Immunology, 2021 Aug; 18(9): 2188-2198.
17. Li N, Tang N, Cheng C, Hu T, Wei X, Han W, Wang H. “Improving the anti-solid tumor efficacy of CAR-T cells by inhibiting adenosine signaling pathway.” OncoImmunology, 2020 Sep 24 ; 9(1): e1824643.
18. Zhang X*, Cheng C*, Sun W, Wang H. “Engineering T Cells Using CRISPR/Cas9 for Cancer Therapy.” Methods Mol Biol, 2020; 2115: 419-433. 
19. Sun W, Wang H. (2020). “Recent advances of genome editing and related technologies in China”. Gene Therapy, 2020 Aug; 27(7-8): 312-320. 
20. An C*, Feng G*, Zhang J, Cao S, Wang Y, Wang N, Lu F, Zhou Q, Wang H. “Overcoming Autocrine FGF Signaling-Induced Heterogeneity in Naive Human ESCs Enables Modeling of Random X Chromosome Inactivation” Cell Stem Cell, 2020 Sep;27(3):482–497.
21. Tang N*, Cheng C*, Zhang X, Qiao M, Li N, Mu W, Wei X, Han W, Wang H. “TGFβ Inhibition via CRISPR Promotes the Long-Term Efficacy of CAR-T Cells Against Solid Tumors” JCI Insight, 2020 Feb;5(4): e133977. 
22. Cao Y*, Sun W*, Wang J, Sheng G, Xiang G, Zhang T, Shi W, Li C, Wang Y, Zhao F#, Wang H^#. “Argonaute proteins from human gastrointestinal bacteria catalyze DNA-guided cleavage of single- and double- stranded DNA at 37 °C.” Cell Discovery, 2019 Jul 30;5:38.
23. Wang H^#，Yang H^#. “Gene-edited babies: What went wrong and what could go wrong.” PLOS Biology, 2019 Apr 30;17(4):e3000224.
24. Mu W*, Tang N*, Cheng C*, Sun W, Wei X, Wang H^#. “In vitro transcribed sgRNA causes cell death by inducing interferon release.” Protein & Cell,2019 Jun;10(6):461-465.
25. Cheng C*, Tang N*, Li J, Cao S, Zhang T, Wei X, Wang H^#. “ Bacteria-free minicircle DNA system to generate integration-free CAR-T cells.” Journal of Medical Genetics, 2019 Jan;56(1):10-17. 
26. Xiang G*, Ren J*, Hai T*, Fu R, Yu D, Wang J, Li W, Wang H^#, Zhou Q^#. “Editing porcine IGF2 regulatory element improved meat production in Chinese Bama pigs.” Cellular and Molecular Life Sciences. 2018 Dec;75(24):4619-4628.  
27. Xiang G, Wang H^#. “Extended pluripotent stem cells facilitate mouse model generation.” Protein & Cell. 2018 Aug 21.doi: 10.1007/s13238-018-0573-0.
28. Mu W, Zhang Y, Xue X, Liu L, Wei X, Wang H^#.” 5′ capped and 3′ polyA-tailed sgRNAs enhance the efficiency of CRISPR-Cas9 system.” Protein & Cell, 2018.Jun;10(3):223–228.
29. Zhang Y, Mu W, Wang H^#. “Gene editing in T cell therapy.” Journal of Genetics and Genomics,  2017 Sep;44 (9) :415-422.
30. Wang H^#. “Editing Base in Mouse Model.” Protein & Cell, 2017 Aug;8(8):558-559.
31. Wang W, Zhang Y, Wang H^#. “Generating Mouse Models Using Zygote Electroporation of Nucleases (ZEN) Technology with High Efficiency and Throughput.” Methods in Molecular Biology, 2017;1605:219-230. 
32. Zhang Y, Zhang X, Cheng C, Mu W, Liu X, Li N, Wei X, Liu X, Xia C, Wang H^#. “CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells.” Frontiers of Medicine, 2017 Dec;11(4):554-562.
33. Xiang G, Zhang X, An C, Cheng C, Wang H^#. “Temperature effect on CRISPR-Cas9 mediated genome editing.” Journal of Genetics and Genomics, 2017 Apr ;44(4):199-205.
34. Liu X, Zhang Y, Cheng C, Cheng WA, Zhang X, Li N, Xia C, Wei X, Liu X, Wang H^#. “CRISPR-Cas9 mediated multiplex gene editing in CAR-T cells.” Cell Research, 2017 Jan;27(1):154-157.
35. Burgess S, Cheng L^#, Gu F, Huang J, Huang Z, Lin S^#, Li J, Li W, Qin W, Sun W, Songyang Z, Wei W^#, Wu Q, Wang H^#, Wang X, Xiong JW, Xi J, Yang H, Zhou B, Zhang B. “Questions about NgAgo” Protein Cell, 2016 Dec;7(12):913-915.
36. Wang W,Kutny PM, Byers SL, Longstaff CJ, DaCosta MJ, Pang C, Zhang Y, Taft RA, Buaas FW, Wang H^#. “Delivery of Cas9 protein into mouse zygotes through a series of electroporation dramatically increased the efficiency of model creation.” Journal of Genetics and Genomics, 2016 May 20;43(5):319-27.
37. Qin W, Kutny PM, Maser RS, Dion SL, Lamont JD, Zhang Y, Perry GA, Wang H^#.“Generating Mouse Models Using CRISPR-Cas9 Mediated Genome Editing.”Current Protocols in Mouse Biology, 2016 Mar 1;6(1):39-66. 
38. Cheng AW*^#, Jillette N*, Lee P, Plaskon D, Fujiwara Y, Wang W, Taghbalout A, Wang H^#. “Casilio: a versatile CRISPR-Cas9-Pumilio hybrid for gene regulation and genomic labeling.” Cell Research, 2016 Feb;26(2):254-7. 
39. Wiles MV, Qin W, Cheng AW, Wang H^#. “CRISPR-Cas9 mediated genome editing and guide RNA design.” Mammalian Genome, 2015 Oct;26(9-10):501-10.
40. Qin W, Dion SL, Kutny PM, Zhang Y, Cheng AW, Jillette NL, Malhotra A, Geurts AM, Chen YG, Wang H^#. “Efficient CRISPR/Cas9-mediated genome editing in mice by zygote electroporation of nuclease.” Genetics, 2015 Jun;200(2):423-30.
41. Theunissen T*, Powell B*, Wang H*, Mitalipova M, Faddah D, Reddy J, Fan Z, Maetzel D, Ganz K, Shi L, Lungjangwa T, Imsoonthornruksa S, Stelzer Y, Rangarajan S, D’Alessio A, Zhang J, Gao Q, Dawlaty M, Young R, Gray N, Jaenisch R. “Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency.”Cell Stem Cell, 2014 Oct 2; 15(4):471-87.
42. Yang H, Wang H, Jaenisch R. “Generating genetically modified mice using CRISPR/Cas-mediated genome engineering.” Nature protocols, 2014 Aug; 9(8):1956-68.
43. Maetzel D*,Sarkar S*, Wang H*, Mosleh LA, Cheng AW, Xu P, Gao Q, Mitalipova M, Jaenisch R. “Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick Type C patient-specific iPS cells.” Stem Cell Reports, 2014 May 15; 2(6):866-80.
44. Cheng AW*, Wang H*, Yang H, Shi L, Katz Y, Rangarajan S, Theunissen TW, Shivalila CS, Dadon DB, Jaenisch R. “Multiplexed activation of endogenous genes by CRISPR-on, a RNA-guided transcriptional activator system.” Cell Research, 2013 October 1; 23(10): 1163-1171.
45. Yang H*, Wang H*, Shivalila CS*, Cheng AW, Shi L, Jaenisch R. “One-step generation of mice carrying reporter and conditional allele by CRISPR/Cas mediated genome editing” Cell, 2013 September 12; 154(6):1370-1379.
46. Faddah D, Wang H, Buganim Y, Cheng AW, Jaenisch R. “Expression of Nanog is biallelic and equally variable as other pluripotency factors.” Cell Stem Cell, 2013 Jul 3;13(1):23-9.
47. Wang H*, Hu YC*, Markoulaki S, Welstead GG, Shivalila CS, Cheng AW, Pyntikova T, Dadon D, Voytas DF, Bogdanove AJ, Page DC, Jaenisch R. “TALEN-mediated editing of the Mouse Y Chromosome.” Nature Biotechnology, 2013 Jun; 31(6):530-2.
48. Wang H*, Yang H*, Shivalila CS*, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. “One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas mediated genome engineering.” Cell, 2013 May 9;153(4):910-8.

真正好的科学研究是充满乐趣和成就感的，希望我们能一起体验科学的魅力。

2024年招生视频：https://mp.weixin.qq.com/s/ehTuLIQEq5v9r1SioC5TsQ