王皓毅，博士，必威精装版app西汉姆联 器官再生與智造全國重點實驗室研究員，基因工程技術研究組組長。長期從事新型基因編輯技術和細胞治療技術開發工作，近年來開發多種新型TnpB小型基因編輯工具和DNA轉座子工具，這些原創性技術的建立為解決基因編輯關鍵“卡脖子”技術對我國相關產業發展的限製提供了重要支撐。在人多能性幹細胞和T細胞中建立了高效的基因編輯方法，開發了多種基因編輯構建增強型和通用型CAR-T細胞策略，並合作開展了基因編輯CAR-T細胞治療實體腫瘤的臨床研究，入選國家引才項目（2015年）。任中國遺傳學會基因編輯分會副主任委員、國際人類可遺傳基因編輯委員會委員。近年來承擔國家重點研發計劃並擔任首席科學家，承擔中科院先導專項子課題和農業農村部項目課題，承擔國家自然科學基金優秀青年基金項目、麵上項目，並獲得國家傑出青年科學基金項目資助。相關研究成果發表在Cell、Nature Biotechnology、Cancer Cell、Cell Stem Cell、Cell Research、Nucleic Acid Research等雜誌上，已發表SCI學術論文八十餘篇，總引用次數過一萬七千餘次 (google scholar統計)。申請中國專利11項，授權3項；申請PCT專利5項，其中一項進入日本獲得授權。

教育經曆：

2003-2009  美國華盛頓大學  分子細胞生物學  博士

2001-2003  美國邁阿密大學  動物學          碩士

1997-2001  廈門大學        生物學          學士

工作經曆 ：

2014 至今  研究員  必威精装版app西汉姆联

2014-2016  傑出訪問教授 美國傑克遜實驗室

2009-2014  博士後  美國麻省理工學院Whitehead研究所

高效和精確的基因工程技術對於生物醫學的研究和應用具有極其重要的價值。研究組的科研興趣在於開發和應用最新的基因工程技術，在人細胞中進行精確的基因修飾與改造。一方麵挖掘開發全新的基因編輯與基因寫入工具，建立全新基因組改造技術；另一方麵應用這些技術在T細胞和幹細胞中進行基因改造，建立新型細胞治療方法。研究組研究方向主要集中在以下兩個方麵:

一 新型基因編輯工具開發 

ZFN、TALEN和CRISPR技術乃至分子生物學中廣泛運用的限製性內切酶和DNA聚合酶等工具酶大部分來自於不同物種的功能基因研究。隨著基因組學的發展，大量新物種的基因組完成測序和組裝，但大量編碼新型蛋白的基因功能未知。我們希望基於數據驅動的研究模式，充分利用人工智能工具和高通量自動化實驗平台，高效挖掘具有成為基因工程新工具潛力的候選係統，然後通過進一步優化，構建具有新功能特性的基因工程新技術，為生物學研究和疾病治療提供更為有力的工具。

二 利用基因編輯技術開發新型細胞治療技術

嵌合抗原受體修飾（chimeric antigen receptor，CAR）T 細胞療法作為全新的腫瘤治療方法在臨床上凸顯出廣闊的應用前景。這些以T細胞為基礎的療法和基因編輯相結合具有重大的應用價值。因此我們在T細胞中優化基因編輯技術，建立新型的細胞治療方法。同時我們也在T細胞中建立進行高通量遺傳學和小分子篩選的技術，以期為免疫治療發現新的治療靶點和藥物。

（*共同第一作者, ^#共同通訊作者）

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.
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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.
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真正好的科學研究是充滿樂趣和成就感的，希望我們能一起體驗科學的魅力。

2024年招生視頻：https://mp.weixin.qq.com/s/ehTuLIQEq5v9r1SioC5TsQ