魏文胜 教授
基因组编辑研究组
北京大学生命科学学院 研究员 博士生导师
电话：
E-mail：wswei@pku.edu.cn
致力于发展基因组编辑技术、功能基因组学以及基因治疗；在此基础上研究癌症、感染等重大疾病发生机制，为发展高效治疗手段提供新的药物靶点和思路。
着重发展真核基因修饰技术 (i.e., TALE & CRISPR system) 及高通量功能基因组学，在此基础上通过多种手段研究人源宿主细胞参与病原微生物感染的蛋白、信号通路及分子机制，为发展宿主导向的治疗手段提供新的药物靶点和思路。在生物技术方面关注真核基因定点修饰、功能基因组学以及基因治疗；在疾病研究方面为癌症与感染性疾病的机制研究提供基础。
利用shRNAmir文库筛选结合高通量测序，获得艰难梭菌毒素蛋白B的候选受体，通过TALEN及CRISPR/Cas9介导的基因敲除，结合生化、免疫及动物实验等多种手段，证明其为人们长期寻找的毒素受体。这项成果对深刻认识这一目前在抗生素抗性相关病菌感染中排名危害第一 (CDC Report，2013) 的梭菌感染机制，具有重大意义。
首次建立了基于CRISPR-Cas9系统的高通量功能性基因筛选技术。利用CRISPR-Cas9系统构建基因敲除文库，实现了大规模基因敲除并应用于高通量功能性筛选。
首次建立了长非编码RNA的高通量功能性筛选新方法。运用CRISPR-Cas9系统，在构建paired-guide RNA(pgRNA) 文库的基础上，实现了长非编码RNA的高通量功能性筛选，并在多个癌细胞系中成功鉴定出调控癌细胞增殖的lncRNA。
成功开发ULtiMATE系统，实现了TALE特别是TALEN载体的快速构建，并此获得了全部TALE重复单元识别DNA碱基的信息。
将基因组编辑技术应用于表观遗传及细胞成像等基础研究，如建立了基于TALE系统的表观组识别技术、利用CRISPR/Cas系统对染色质进行实时成像等。
Yi ZY , Zhang XX , Tang W , Yu Y , Wei XX, Zhang X, Wei WS. (2024) Strand-selective base editing of human mitochondrial DNA using mitoBEs. Nat. Biotechnol., 42: 498-509.
Wu ZG , Lamao Q, Gu MC, Jin XX, Liu Y, Tian F, Yu Y, Yuan PF, Gao SX, Fulford TS, Uldrich AP, Wong CCL, Wei WS. (2024) Unsynchronized butyrophilin molecules dictate cancer cell evasion of Vγ9Vδ2 T-cell killing. Cell. Mol. Immunol., 21: 362-373.
Yi ZY, Zhang XX , Wei XX, Li JY, Ren JW, Zhang X, Zhang YK, Tang HX, Chang XW, Yu Y, Wei WS. (2024) Programmable DNA pyrimidine base editing via engineered uracil-DNA glycosylase. Nat. Commun., 15: 6397.
Bao Y, Wei WS. (2024) Protocol for high-throughput screening of functional lysine residues in cell fitness. STAR Protoc., 5: 103418.
Zhang XX, Yi ZY, Tang W, Wei WS. (2024) Streamlined process for effective and strand-selective mitochondrial base editing using mitoBEs. Biophys. Rep., 10: 191-200.
Pan Q, Zhang ZX, Xiong YF, Bao Y, Chen TX, Xu P, Liu ZH, Ma HZ, Yu Y, Zhou Z, Wei WS. (2024) Mapping functional elements of the DNA damage response through base editor screens. Cell Rep., 43: 115047.
He X, Liu YS, Gao X, Tang FY, Tian YX, Gong SY, Shen J, Wang AM, Sun LQ, Wei WS, Weng L. (2024) N-terminal acetylation of transcription factor LIP induces immune therapy resistance via suppression of PD-L1 expression in non-small cell lung cancer. J ImmunoTher. Cancer, 12: e009905.
Yi ZY, Zhao YX, Yi ZX, Zhang YJ, Tang GB, Zhang XX, Tang HX, Zhang W, Zhao Y, Xu HY, Nie YY, Sun XQ, Xing LJ, Dai L, Yuan PF, Wei WS. (2023) Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice. Genome Biol., 24: 243.
Bao Y, Pan Q, Xu, Liu ZH, Zhang ZX, Liu YS, Xu YY, Yu Y, Zhou Z, Wei WS. (2023) Unbiased interrogation of functional lysine residues in human proteome. Mol. Cell, 83: 4614-4632.
Ma KY, Wang X, Wu LJ, Yu LL, Ye JH, Li XL, Geng LL, Shi ZY, Yang HH, Zhang XJ, Zhang YJ, Wu SC, Yuan PF, Zhang YC, Dong F, Hao S, Hu LP, Wei WS, Fang RG, Cheng T. (2023) CEA cell adhesion molecule 5 enriches functional human hematopoietic stem cells capable of long-term multi-lineage engraftment. iScience, 26: 108561.
Mi L, Shi M, Li Y.X., Xie G, Rao X, Wu D, Cheng A, Niu M, Xu F, Yu Y, Gao N, Wei WS, Wang X, Wang Y. (2023) DddA homolog search and engineering expand sequence compatibility of mitochondrial base editing. Nat. Commun. 14: 874.
Yi ZY, Qu L, Tang HX, Liu ZH, Liu Y, Tian F, Wang CH, Zhang XX, Feng ZQ, Yu Y, Yuan PF, Yi ZX, Zhao YX, Wei WS. (2022) Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nat. Biotechnol., 40: 946-955.
Lu SY, Yang CY, Tang C, Yang Y, Yu WH, Wang JB, Zhou YN, Huang Q, Yisimayi AYJ, Liu S, Huang WJ, Cao YL, Wang YC, Zhou Z, Peng XZ, Wang JW, Xie XL, Wei WS. (2022) Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell, 185: 1728-1744.
Liu Y, Ding B, Zheng LN, Xu P, Liu ZH, Chen Z, Wu PY, Zhao Y, Pan Q, Guo Y, Wang W, Wei WS. (2022) Regulatory elements can be essential for maintaining broad chromatin organization and cell viability. Nucl. Acids Res., 50: 4340-4354.
Wei WS, Gao CX. (2022) Gene editing: from technologies to applications in research and beyond. Sci. China-Life Sci., 65: 657-659.
Li GL, Li XY, Zhuang SK, Wang LR, Zhu YF, Chen YC, Sun W, Wu ZG Zhou Z, Chen J, Huang XX, Wang J, Li DL, Li W Wang HY, Wei WS. (2022) Gene editing and its applications in biomedicine. Sci. China-Life Sci., 65: 660-700.
Guo SJ, Chen YO, Liu JZ, Zhang XY, Liu ZH, Zhou Z, Wei WS. (2022) Low-density lipoprotein receptor-related protein 1 is a CROPs-associated receptor for Clostridioides difficile toxin B. Sci. China-Life Sci., 65: 107-118.
Zhu SY, Liu Y, Zhou Z, Zhang ZY, Xiao X, Liu ZH, Chen A, Dong XJ, Tian F, Chen SH, Xu YY, Wang CH, Li QH, Niu XR, Pan Q, Du S, Xiao JY, Wang JW,Wei WS. (2022) Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry.Sci. China-Life Sci., 65: 701-717.
Xu P Liu ZH, Liu Y, Ma HZ, Xu YY, Bao Y, Zhu SY, Cao ZZ, Wu ZG, Zhou Z,Wei WS. (2021) Genome-wide interrogation of gene functions through base editor screens empowered by barcoded sgRNAs.Nat. Biotechnol., 39: 1403-1413.
Zhou Z, Zhang XY, Lei XB, Xiao X, Jiao T, Ma RY, Dong XJ, Jiang Q, Wang WJ, Shi YJ, Zheng T, Rao J, Xiang ZC, Ren LL, Deng T, Jiang ZF, Dou ZX,Wei WS, Wang JW. (2021) Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection.Signal Transduct. Target. Ther., 6: 382.
Ding B, Liu Y, Liu ZH, Zheng LN, Xu P, Chen Z, Wu PY, Zhao Y, Pan Q, Guo Y,Wei WS, Wang W. (2021) Noncoding loci without epigenomic signals can be essential for maintaining global chromatin organization and cell viability.Sci. Adv., 7: eabi6020.
Liang YS, Zhang GG, Li QH, Han L, Hu XY, Guo Y, Tao WY, Zhao XM, Guo MZ, Gan TY, Tong YM, Xu YF, Zhou Z, Ding Q,Wei WS, Zhong J. (2021) TRIM26 is a critical host factor for HCV replication and contributes to host tropism.Sci. Adv., 7: eabd9732.
Liu Y, Liu ZH, Cao ZZ,Wei WS. (2020) Reply to: Fitness effects of CRISPR/Cas9-targeting of long noncoding RNA genes.Nat. Biotechnol.,38: 577-578.
牛煦然，周卓，魏文胜. (2020) 浅谈2020年诺贝尔化学奖：通向未来的基因编辑。大学化学，35: 118–126.
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