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左二伟课题组

左二伟课题组

Zuo Erwei Lab

  首席科学家/课题组长介绍:

  左二伟,研究员,课题组组长。2015年获得广西大学动物繁殖学博士,2015年至2018年,中国科学院神经科学研究所非人灵长类研究组从事博后工作。长期从事动物遗传育种繁殖和基因编辑技术的相关研究。以第一作者身份在国内外高水平期刊Science、Cell Research、Genome biology等发表文章。

  Erwei Zuo, Principal Investigator. He obtained his Ph.D. from Guangxi University, where he studied the animal reproduction science. His postdoctoral training was at the Institute of Neuroscience (ION) of Chinese Academy of Sciences (CAS),where he was dedicated to animal genetic breeding and gene editing related research. He has became an independent investigator at the Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Sciences since 2018. His lab aims to explore genome editing and other potential applications for CRISPR-Cas systems.

 

  团队研究方向: 

  主要研究哺乳动物的基因编辑方法。(1)通过干细胞技术提高基因工程猪生产效率。(2)通过研究对现有的基因编辑手段进行改进,以扩大其应用范围,提高特异性,减少脱靶效应。(3)通过基因组水平的编辑手段构建各种动物研究模型,包括小鼠、猪等哺乳动物的疾病模型。

  Gene editing methods and technology in mammalian animals. (1) Improving reproductive efficiency of genetic engineering pigs by using stem cell. (2) Optimization of gene editing technology, including broadening the application scope, improving specificity, and reducing off-target effect. (3) Construction of animal disease models in mice and pigs by genomic manipulation.

 

  研究进展:

  团队建立了一种名为GOTI的新型脱靶检测技术,并使用该技术发现新兴的单碱基编辑技术有可能导致无法预测的脱靶,存在严重的安全风险。此研究显著提高基因编辑技术的脱靶检测灵敏性,并不借助于脱靶位点预测技术,可检测之前手段无法发现的完全随机的脱靶位点,为基因编辑工具的安全性评估带来了突破性的新工具,有望成为新的行业检测标准。

  We developed a method named “GOTI”, and found that cytosine base editor induced substantial off-target single nucleotide variants (SNVs). GOTI significantly improved the sensitivity of off-target detection without prediction in advance and could also detect randomly generated off-target variants. Thus, GOTI has provided as a new breathtaking method for the safety evaluation of genome editing tools, which could be taken as industry standard.

  

  研究成果:

1. Yuan,T.*, Yan,N.*, Fei,T.*, Zheng,J.*, Meng,J.*, Li,N.*, Liu,J.*, Zhang,H., Xie,L., Ying,W., Li,D., Shi,L., Sun,Y.,Li,Y., Li,Y., Sun,Y.# and Zuo,E.#.(2021). Optimization of C-to-G base editors with sequence context preference predictable by machine learning methods.Nature Communications: 12:4902

2. Xue,Y.*, Hu,X.*,Wang,D.*, Li,D.*,Li,Y.,Wang,F.,Huang,M., Gu,X., Xu,Z., Zhou,J., Wang,J., Chai,R., Shen,J., Chen,Z., Li,G., Yang,H., Li,H.#, Zuo,E.# and Shu,Y.#. (2021).Gene editing in a Myo6 semi-dominant mouse model rescues auditory function Author links open overlay panel .Molecular Therapy. DOI: 10.1016/j.ymthe.2021.06.015

3. Zhang,J.*, E,M.Khazalwa.*, H, M.Abkallo., Zhou,Y., Nie,X., Ruan,J., Zhao,C., Wang,J., Xu,J., Li.X., Zhao,S., Zuo,E.#, L,Steinaa#.and Xie,S.#.(2021).The Advancements, Challenges and Future Implications of the CRISPR/Cas9 System in Swine Research.Journal of Genetics and Genomics:48(5).347-360.
4. Wei,Y.*, Zhou, Y.*, Liu,Y.*, Ying,W., Lv,R., Zhao,Q.,  Zhou,H., Zuo,E.#,  Sun,Y.#, Yang,H.# and Zhou,C,#. (2021). Indiscriminate ssDNA cleavage activity of CRISPR-Cas12a induces no detectable off-target effects in mouse embryos.Protein & Cell . DOI: 10.1007/s13238-021-00824-z

5. Huang, X.*, Lv, J.,*, Li, Y.*, Mao, S., Li, Z., Jing, Z., Sun, Y., Zhang,X., Shen, S., Wang, X., Di, M., Ge, J., Huang, X., Zuo,E.# and Chi, T.#.(2020). Programmable C-to-U RNA editing using the human APOBEC3A deaminase .The EMBO Journal:39:e104741.

6. Zuo,E.*, Sun,Y. *, Wei,Wu.*, Yuan ,T.*, Ying,W., Sun,H., Yuan,L., Lars M. Steinmetz # , Li,Y.# and Yang,H.#.(2020).GOTI, a method to identify genome-wide off-target effects of genome editing in mouse embryos.Natrue Protocols:15.3009–3029.

7. Lee,S.*, Ding,N.*, Sun,Y., Yuan,T., Li,J., Yuan,Q., Liu,L.,Yang,J.,Wang,Q., Anatoly B. Kolomeisky, Isaac B. Hilton, Zuo,E.# and Gao,X.#. (2020).Single C-to-T substitution using engineered  APOBEC3G-nCas9 base editors with minimum  genome- and transcriptome-wide off-target effects.Science Advance:29(6).1773.

8. Zuo,E.*#, Sun,Y.*, Yuan ,T.* , He,B.* , Zhou,C.* , Ying,W., Liu,L., Wei ,W., Zeng,R., Li,Y.# and Yang,H.#.(2020).A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects.Nature Methods:17(6):600–604.

9. Lin X.*, Chen H.*, Lu Y.*, Hong S.*, Hu X.*, Gao Y., Lai L., Li J., Wang Z., Ying W., Ma L., Wang N., Zuo,E.#, Yang H.# and Chen W. #.(2020).Base editing-mediated splicing correction therapy for spinal muscular atrophy. Cell Research:0:1-3. 30(6).

10. Deng K.*, Feng W.*, Liu X.*, Su X., Zuo,E., Du S., Huang Y., Shi D. # and Lu,F. # .(2020).Anti-silencing Factor 1A is Associated with Genome Stability Maintenance of Mouse Preimplantation Embryos.Biology of Reproduction:102(4),817-827.

11. Li J. *, Lin X. *, Tang C. *, Lu Y. *, Hu X. *, Zuo,E., Li H., Ying W., Sun Y. , Lai L., Chen H., Guo X., Zhang Q., Wu S., Zhou C., Shen X., Wang Q., Lin ., Ma L., Wang N.,Ad.Krainer, Shi L.#, Yang H.# and Chen W.#.(2020) .Disruption of splicing-regulatory elements using CRISPR/Cas9 to rescue spinal muscular atrophy in human iPSCs and mice.National Science Review:7(1),92-101.

12. Zhao, X., Wei, W., Pan,H., Nie,J., Chen,D., Zhang,P., Chen, F., Fu, Q,. Zuo, E.#, Lu, Y.# and Zhang, M.#. (2019). Identification of the Sex of Pre-implantation Mouse Embryos Using a Marked Y Chromosome and CRISPR/Cas9. SCIENTIFIC REPORTS:9: 14315.

13. Li,J.* , Hong,S.*, Chen,W.#, Zuo,E.# and Hui Yang#.(2019) . Advances in detecting and reducing off-target effects generated by CRISPR-mediated genome editing.Journal of Genetics and Genomics:46,513-521.

14. Wang, X.*, Kang, J.*, Wei, L.*, Yang, X.*, Sun, H., Yang, S., Lu, L., Yang, M., Bai, M., Chen, Y., Long, J., Li, N., Li, D., Huang, J., Lei, M., Shao, Z., Yuan, W.#, Zuo, E.#, Lu, K. #, Liu, M.# and Li, J#. (2019). PHF7 is a novel histone H2A E3 ligase prior to histone-to-protamine exchange during spermiogenesis. Development: dev.175547.

15. Zhou, C.*, Sun, Y.*, Yan, R.*, Liu, Y.*, Zuo, E.*, Gu, C., Han, L., Wei, Y., Hu, X., Zeng, R., Li, Y.#, Zhou, H.#, Guo, F.# and Yang, H.# .(2019).Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis. Nature:571, 275–278.

16. Zuo, E.*, Sun, Y.*, Wei, W.*, Yuan, T.*, Ying, W., Sun, H., Yuan, L., Steinmetz, L. M.#, Li, Y.# and Yang, H#.(2019). Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science:364, 289-292.

17. Zuo, E.*, Huo, X.*, Yao, X.*, Hu, X.*, Sun, Y.*, Yin, J*., He, B., Wang, X., Shi, L., Ping, J., Wei, Y., Ying, W., Wei, W., Liu, W., Tang, C., Li, Y., Hu, J.# and Yang, H.#. (2017).CRISPR/Cas9-mediated targeted chromosome elimination. Genome Biology:18:224.

18. Zuo, E.*, Cai, Y. J.*, Li, K.*, Wei, Y.*, Wang, B. A.*, Sun, Y.*, Liu, Z., Liu, J., Hu, X., Wei, W., Huo, X., Shi, L., Tang, C., Liang, D., Wang, Y., Nie, Y. H., Zhang, C. C., Yao, X., Wang, X., Zhou, C., Ying, W., Wang, Q., Chen, R. C., Shen, Q., Xu, G. L., Li, J., Sun, Q., Xiong#, Z. Q.# and Yang, H#.(2017).One-step generation of complete gene knockout mice and monkeys by CRISPR/Cas9-mediated gene editing with multiple sgRNAs. Cell Research:27, 933-945.

19. Wang,L. *, Li,M. *, Qu, C.,Miao,W., Yin,Q., Liao,J., Cao,H., Huang,M., Wang,K. Zuo,E. , Peng,G., Zhang,S., Chen,G., Li,Q., Tang,K., Yu, Q., Li,Z., Catherine CL Wong, Xu,G., Jing, N.,Yu,X.,# and Li,J.#.(2017).CRISPR-Cas9-mediated genome editing in one blastomere of two-cell embryos reveals a novel Tet3 function in regulating neocortical development.Cell Research:1-15.

20. Zuo, E. *, Yang, X.#, Lu, Y., Xie, L., Shang, J., Li, D., Yang, H., Hu, L., Zhao, H., Lu, S., Lu, K.#.(2015). ZPAC is required for normal spermatogenesis in mice. Mol. Reprod:Dev. 82: 747-755.

21. Zhang, M.*, Zhou, H., Zheng, C. ,Xiao, J. , Zuo, E., Liu, W., Xie, D.,Shi, Y.,Wu, C., Wang, H. , Li, D. & Li, J .#.(2014).The Roles of Testicular C-kit Positive Cells in De novo Morphogenesis of Testis. SCIENTIFIC REPORTS:4 : 5936.

22. Liu,H.*, Lv,P., Zhu,X., Wang,X., Yang,X., Zuo,E., Lu,Y., Lu, S., Lu,K.#.(2014).In vitro development of porcine transgenic nuclear-transferred embryos derived from newborn Guangxi Bama mini-pig kidney fibroblasts.In Vitro Cell.Dev.Biol.—Animal:50:811–821.

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