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李伟 研究员

基因工程技术和细胞/动物模型

欢迎您的加入干细胞与细胞周期调控研究组！
- 工作人员：李伟、李天达、李治琨、何正泉
- 博士后：崔彤彤、刘超、刘晶晶、毛伊幻、滕飞、胡艳萍、高婷婷、任吉龙
- 研究生：戴墨雨、郭玮琪、李沛琪、Najmeh Karimi、李镕岐、梁晨、刘莎莎、毛邦炜、孙雪寒、王琳、徐静、杨宁、张锦、赵玉龙、周丽、朱骊宇

 
 

　　基因组信息及其表达调控是生命多样性和复杂性的重要基础，也是疾病治疗和健康干预的重要靶标和手段。我们特别感兴趣结合基因工程、细胞工程和合成生物学等手段建立新的基因工程技术和细胞/动物模型，用于（1）揭示生殖与再生相关性状及其种间进化差异的调控机制；（2）设计和制造功能定制化的细胞；（3）重大疾病的基因治疗。



拥有独特染色体组型的染色体连接小鼠



CDetection实现DNA的快速精准检测



通过筛选优化crRNA骨架，有效提高Cas12a的编辑效率



通过人工合成gRNA骨架进一步拓展Cas12b/C2c1基因编辑工具盒



破坏细胞机械收缩促进成纤维细胞向神经元转分化的过程。



开发新型蛋白质工程化改造的方法，获得高效基因组编辑工具Cas12i

 

研究内容和目标:
我组主要从事基因工程和干细胞等创新生物技术的研发，并利用这些新技术和模型揭示哺乳动物生殖与再生的基础调控规律，开发重大疾病的基因治疗。

 

代表性发表论文:

  1. Cui T#, Cai B#, Tian Y, Liu X, Liang C, Gao Q, Li B, Ding Y, Li R, Zhou Q, Li W*, Teng F*. Therapeutic In Vivo Gene Editing Achieved by a Hypercompact CRISPR-Cas12f1 System Delivered with All-in-One Adeno-Associated Virus. Advanced Science (Weinh) 2024 Feb 26:e2308095. doi: 10.1002/advs.202308095. Online ahead of print.
  2. Wang C#, Fang S#, Chen Y#, Tang N, Jiao G, Hu Y, Li J, Shan Q, Wang X, Feng G, Zhou Q*, Li W*. High-efficiency targeted transgene integration via primed micro-homologues. Cell Discovery 2023 Jul 4;9(1):69. doi: 10.1038/s41421-023-00552-0.
  3. Wang LB#, Li ZK#, Wang LY#, Xu K#, Ji TT#, Mao YH, Ma SN, Liu T, Tu CF, Zhao Q, Fan XN, Liu C, Wang LY, Shu YJ, Yang N, Zhou Q*, Li W*. A sustainable mouse karyotype created by programmed chromosome fusion. Science 2022 Aug 26;377(6609):967-975. doi: 10.1126/science.abm1964. Epub 2022 Aug 25.
  4. He ZQ#, Li YH#, Feng GH#, Yuan XW#, Lu ZB#, Dai M, Hu YP, Zhang Y, Zhou Q*, Li W*. Pharmacological Perturbation of Mechanical Contractility Enables Robust Transdifferentiation of Human Fibroblasts into Neurons. Advanced Science (Weinh). 2022 May;9(13):e2104682. doi: 10.1002/advs.202104682.
  5. Chen Y#, Hu Y#, Wang X#, Luo S, Yang N, Chen Y, Li Z, Zhou Q*, Li W*. Synergistic engineering of CRISPR-Cas nucleases enables robust mammalian genome editing. Innovation (Camb). 2022 May 26;3(4):100264. doi: 10.1016/j.xinn.2022.100264.
  6. Guo L#, Sun X#, Wang X#, Liang C#, Jiang H#, Gao Q#, Dai M#, Qu B, Fang S, Mao Y, Chen Y, Feng G, Gu Q, Wang RR*, Zhou Q*, Li W*. SARS-CoV-2 detection with CRISPR diagnostics. (2020) Cell Discovery 6:34. doi: 10.1038/s41421-020-0174-y.
  7. Wang LY#, Li ZK#, Wang LB#, Liu C#, Sun XH, Feng GH, Wang JQ, Li YF, Qiao LY, Nie H, Jiang LY, Sun H, Xie YL, Ma SN, Wan HF, Lu FL*, Li W*, Zhou Q*. Overcoming Intrinsic H3K27me3 Imprinting Barriers Improves Post-implantation Development after Somatic Cell Nuclear Transfer. (2020) Cell Stem Cell 27(2):315-325.e5. doi: 10.1016/j.stem.2020.05.014.
  8. Qu B#, Wu S#, Jiao G#, Zou X#, Li Z#, Guo L#, Sun X, Huang C, Sun Z, Zhang Y, Li H, Zhou Q, Sui R*, Li W*. Treating Bietti crystalline dystrophy in a high-fat diet-exacerbated murine model using gene therapy. (2020) Gene Therapy 27(7-8):370-382.doi: 10.1038/s41434-020-0159-3.
  9. Teng F#, Guo L#, Cui T, Wang XG, Xu K, Gao Q, Zhou Q*, Li W*. CDetection: CRISPR-Cas12b-based DNA detection with sub-attomolar sensitivity and single-base specificity. (2019) Genome Biology 20(1):132. doi: 10.1186/s13059-019-1742-z.
  10. Teng F#, Li J#, Cui T#, Xu K, Guo L, Gao Q, Feng G, Chen C, Han D, Zhou Q*, Li W*. Enhanced mammalian genome editing by new Cas12a orthologs with optimized crRNA scaffolds. (2019) Genome Biology 20(1):15. doi: 10.1186/s13059-019-1620-8.
  11. Wang J#, Wang L#, Feng G#, Wang Y#, Li Y, Li X, Liu C, Jiao G, Huang C, Shi J, Zhou T, Chen Q, Liu Z, Li W*, Zhou Q*. Asymmetric Expression of LincGET Biases Cell Fate in Two-Cell Mouse Embryos. (2018) Cell 175(7):1887-1901.e18. doi: 10.1016/j.cell.2018.11.039.
  12. Teng F#, Cui T#, Feng G, Guo L, Xu K, Gao Q, Li T, Li J, Zhou Q, Li W*. Repurposing CRISPR-Cas12b for mammalian genome engineering. (2018) Cell Discovery 4:63. doi: 10.1038/s41421-018-0069-3.
  13. Zhang W#, Wan H#, Feng G#, Qu J#, Wang J, Jing Y, Ren R, Liu Z, Zhang L, Chen Z, Wang S, Zhao Y, Wang Z, Yuan Y, Zhou Q, Li W*, Liu G*, Hu B*. SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. (2018) Nature 560(7720):661-665. doi: 10.1038/s41586-018-0437-z.
  14. Li ZK#, Wang LY#, Wang LB#, Feng GH#, Yuan XW#, Liu C, Xu K, Li YH, Wan HF, Zhang Y, Li YF, Li X, Li W*, Zhou Q*, Hu BY*. Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions. (2018) Cell Stem Cell 23(5):665-676.e4. doi: 10.1016/j.stem.2018.09.004.
  15. Xu K#, Yang Y#, Feng GH#, Sun BF#, Chen JQ#, Li YF, Chen YS, Zhang XX, Wang CX, Jiang LY, Liu C, Zhang ZY, Wang XJ, Zhou Q*, Yang YG*, Li W*. Mettl3-mediated m6A regulates spermatogonial differentiation and meiosis initiation. (2017) Cell Research 27(9):1100-1114. doi: 10.1038/cr.2017.100. (Cover story)
  16. Li X#, Cui XL#, Wang JQ#, Wang YK, Li YF, Wang LY, Wan HF, Li TD, Feng GH, Shuai L, Li ZK, Gu Q, Hao J, Wang L, Zhao XY, Liu ZH, Wang XJ, Li W*, Zhou Q*. Generation and application of mouse-rat allodiploid embryonic stem cells. (2016) Cell 164(1-2):279-292. doi: 10.1016/j.cell.2015.11.035.
  17. Wan HF#, Feng CJ#, Teng F#, Yang SH#, Hu BY, Niu YY, Xiang P, Fang WZ, Ji WZ, Li W*, Zhao XY*, Zhou Q*. One-step generation of p53 gene biallelic mutant Cynomolgus monkey via the CRISPR/Cas system. (2015) Cell Research 25(2):258-261. doi: 10.1038/cr.2014.158.
  18. Li W#, Li X#, Li TD#, Jiang MG#, Wan HF, Luo GZ, Feng CJ, Cui XL, Teng F, Yuan Y, Zhou Q, Gu Q, Shuai L, Sha JH, Xiao YM, Wang L, Liu ZH, Wang XJ, Zhao XY, Zhou Q*. Genetic modification and screening in rat using haploid embryonic stem cells. (2014) Cell Stem Cell 14(3):404-414. doi: 10.1016/j.stem.2013.11.016.
  19. Li W#, Teng F#, Li T, Zhou Q*. Simultaneous generation and germline transmission of multiple gene mutations in rat using CRISPR-Cas systems. (2013) Nature Biotechnology 31(8):684-686. doi: 10.1038/nbt.2652.
  20. Li W#, Shuai L#, Wan H#, Dong M#, Wang M, Sang L, Feng C, Luo GZ, Li T, Li X, Wang L, Zheng QY, Sheng C, Wu HJ, Liu Z, Liu L, Wang L, Wang XJ, Zhao XY*, Zhou Q*. Androgenetic haploid embryonic stem cells produce live transgenic mice. (2012) Nature 490(7420):407-411. doi: 10.1038/nature11435.