Group of DNA Repair, Gene Editing & Gene Therapy
Principal investigator
Name:
Jia ChenAssociate Professor , PhD, Associate Professor
Position:
Affiliation:
School of Life Science and Technology
Honor:
Education Background:
- 1998/09-2002/06, College of Life Science, Nankai University, BS
- 2002/09-2009/04, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, PhD
Working Experience:
- 2009/07-2014/06, National Institutes of Health, Postdoc Fellow
- 2014/11-2019/09, School of Life Science and Technology, ShanghaiTech University, Assistant Professor (TENURE-TRACK)
- 2019/10-Now, School of Life Science and Technology, ShanghaiTech University, Associate Professor (Tenured)
Group Introduction
Research Area:
DNA Repair, Gene Editing and Gene Therapy
Research Interests:
Species survival is closely related to genome stability, which is monitored and maintained by DNA repair systems. However, cell can initiate error-prone DNA repair in various physiological and pathological conditions. Thus, the fidelity of DNA repair affects disease, aging and evolution. Genome editing is a type of genetic engineering, by which DNA is inserted, deleted or replaced in the genome of a living organism. Genome editing tools can be broadly applied in life science research and biomedicine. Though CRISPR/Cas gene editing system is efficient in gene knockout, the efficiency of CRISPR/Cas-mediated precise editing is usually low. Recently, novel gene editing systems, including base editor and prime editor, which combine nucleotide deaminase and reverse transcriptase respectively with the CRISPR/Cas system, have been developed with high editing efficiency and precision. Our lab focuses on DNA repair-induced mutagenesis, the development and application of new gene editing systems and gene ediitng therapy. We are particularly interested in: 1) DNA repair-induced mutagenesis in gene editing, carcinogenesis and aging; 2) Development of new gene editing tools; 3) Gene editing therapy for human disease.
Research Achievement
Our lab revealed the mechanism of APOBEC cytidine deaminase-mediated mutagenesis during the repair of CRISPR/Cas9-generated DNA breaks. We developed multiple series of base editors, including enhanced base editors (eBEs) with improved product purity and efficiency, dCpf1 base editors (dCpf1-BEs) for editing in A/T-rich regions, human APOBEC3A base editors (hA3A-BEs) for efficient editing in G/C-rich and/or highly methylated regions, dCas12a-derived base editors (BEACON) for efficient editing with only background levels of DNA damage response and transformer base editors (tBEs) for eliminating gRNA-dependent and gRNA-independent off-target mutations. We also determined the genome-wide and transcriptome-wide off-target effects by prime editor 3 (PE3) and developed sPE and aPE systems with improved editing efficiency.
Representative Publications (*First Author, # Corresponding Author)
- 1. Li, Xiaosa#*; Zhou, Lina*; Gao, Bao Qing*; Li, Guangye; Wang, Xiao; Wang, Ying; Wei, Jia; Han, Wenyan; Wang, Zixian; Li, Jifang; Gao, Runze; Zhu, Junjie; Xu, Wenchao; Wu, Jing; Yang, Bei; Sun, Xiaodong#; Yang, Li#; Chen, Jia#.Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure.NATURE COMMUNICATIONS. Mar 2022. 13(1):1669.
- 2. Gao, Runze*; Fu, Zhi-Can*; Li, Xiangyang*; Wang, Ying*; Wei, Jia; Li, Guangye; Wang, Lijie; Wu, Jing; Huang, Xingxu#; Yang, Li#; Chen, Jia#.Genomic and Transcriptomic Analyses of Prime Editing Guide RNA-Independent Off-Target Effects by Prime Editors.CRISPR JOURNAL. Apr 2022. 5(2):276-293.
- 3. Li, Guanglei*; Li, Xiangyang*; Zhuang, Songkuan*; Wang, Liren*; Zhu, Yifan*; Chen, Yangcan*; Sun, Wen*; Wu, Zeguang*; Zhou, Zhuo; Chen, Jia#; Huang, Xingxu#; Wang, Jin#; Li, Dali#; Li, Wei#; Wang, Haoyi#; Wei, Wensheng#*.Gene editing and its applications in biomedicine.SCIENCE CHINA-LIFE SCIENCES. Apr 2022. 65(4):660-700.
- 4. Wang, Lijie*; Xue, Wei*; Zhang, Hongxia*; Gao, Runze*; Qiu, Houyuan*; Wei, Jia; Zhou, Lina; Lei, Yun-Ni; Wu, Xiaocheng; Li, Xiao; Liu, Chengfang; Wu, Jing; Chen, Qiubing; Ma, Hanhui; Huang, Xingxu; Cai, Cheguo; Zhang, Ying; Yang, Bei#; Yin, Hao#; Yang, Li#; Chen, Jia#.Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations.NATURE CELL BIOLOGY. May 2021. 23(5):552-563.
- 5. Yang, Li#*; Chen, Jia#.A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing.TRENDS IN BIOCHEMICAL SCIENCES. Oct 2020. 45(10):874-888.
- 6. Wang, Xiao*; Ding, Chengfeng*; Yu, Wenxia*; Wang, Ying*; He, Siting*; Yang, Bei*; Xiong, Yi-Chun; Wei, Jia; Li, Jifang; Liang, Jiayi; Lu, Zongyang; Zhu, Wei; Wu, Jing; Zhou, Zhi; Huang, Xingxu; Liu, Zhen#; Yang, Li#; Chen, Jia#.Cas12a Base Editors Induce Efficient and Specific Editing with Low DNA Damage Response.CELL REPORTS. Jun 2020. 31(9).
- 7. Yang, Li#*; Yang, Bei#; Chen, Jia#.One Prime for All Editing.CELL. Dec 2019. 179(7):1448-1450.
- 8. Wang, Ying*; Gao, Runze*; Wu, Jing*; Xiong, Yi-Chun; Wei, Jia; Zhang, Sipin; Yang, Bei; Chen, Jia#; Yang, Li#.Comparison of cytosine base editors and development of the BEable-GPS database for targeting pathogenic SNVs.GENOME BIOLOGY. Oct 2019. 20(1).
- 9. Chen, Jia#*; Yang, Bei#; Yang, Li#.To BE or not to BE, that is the question.NATURE BIOTECHNOLOGY. May 2019. 37(5):520-521.
- 10. Yang, Bei#*; Yang, Li#; Chen, Jia#.Development and Application of Base Editors.CRISPR JOURNAL. Apr 2019. 2(2):91-104.
- 11. Li, Jianan*; Liu, Zhen*; Huang, Shisheng*; Wang, Xiao; Li, Guanglei; Xu, Yuting; Yu, Wenxia; Chen, Shanshan; Zhang, Yu; Ma, Hanhui; Ke, Zunfu; Chen, Jia#; Sun, Qiang#; Huang, Xingxu#.Efficient base editing in G/C-rich regions to model androgen insensitivity syndrome.CELL RESEARCH. Feb 2019. 29(2):174-176.
- 12. Wang, Xiao*; Li, Jianan*; Wang, Ying*; Yang, Bei*; Wei, Jia*; Wu, Jing; Wang, Ruixuan; Huang, Xingxu#; Chen, Jia#; Yang, Li#.Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion.NATURE BIOTECHNOLOGY. Oct 2018. 36(10):946-949.
- 13. Pawluk, April#*; Chen, Jia; Ji, Weizhi; Mali, Prashant.The Future of Genome Editing.CELL. May 2018. 173(6):1311-1313.
- 14. Li, Xiaosa*; Wang, Ying*; Liu, Yajing*; Yang, Bei*; Wang, Xiao; Wei, Jia; Lu, Zongyang; Zhang, Yuxi; Wu, Jing; Huang, Xingxu#; Yang, Li#; Chen, Jia#.Base editing with a Cpf1-cytidine deaminase fusion.NATURE BIOTECHNOLOGY. Apr 2018. 36(4):324-327.
- 15. Lei, Liqun*; Chen, Hongquan*; Xue, Wei*; Yang, Bei*; Hu, Bian*; Wei, Jia; Wang, Lijie; Cui, Yiqiang; Li, Wei; Wang, Jianying; Yan, Lei; Shang, Wanjing; Gao, Jimin; Sha, Jiahao; Zhuang, Min; Huang, Xingxu; Shen, Bin#; Yang, Li#; Chen, Jia#.APOBEC3 induces mutations during repair of CRISPR-Cas9-generated DNA breaks.NATURE STRUCTURAL & MOLECULAR BIOLOGY. Jan 2018. 25(1):45-52.
- 16. Wang, Lijie*; Xue, Wei*; Yan, Lei*; Li, Xiaosa; Wei, Jia; Chen, Miaomiao; Wu, Jing; Yang, Bei#; Yang, Li#; Chen, Jia#.Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor.CELL RESEARCH. Oct 2017. 27(10):1289-1292.
- 17. Yang, Bei#*; Li, Xiaosa; Lei, Liqun; Chen, Jia#.APOBEC: From mutator to editor.JOURNAL OF GENETICS AND GENOMICS. Sep 2017. 44(9):423-437.
- 18. Chen, Jia*; Miller, Brendan F.; Furano, Anthony V.#.Repair of naturally occurring mismatches can induce mutations in flanking DNA.ELIFE. 2014. 3.
- 19. Hu, Guang-Jing*; Chen, Jia*; Zhao, Xiao-Nan*; Xu, Jia-Jia; Guo, Dong-Qing; Lu, Ming; Zhu, Ming; Xiong, Ying; Li, Qin; Chang, Catherine C. Y.; Song, Bao-Liang; Chang, Ta-Yuan; Li, Bo-Liang#.Production of ACAT1 56-kDa isoform in human cells via trans-splicing involving the ampicillin resistance gene.CELL RESEARCH. 2013. 23(8):1007-1024.
- 20. Chen, Jia*; Zhao, Xiao-Nan*; Yang, Li; Hu, Guang-Jing; Lu, Ming; Xiong, Ying; Yang, Xin-Ying; Chang, Catherine C. Y.; Song, Bao-Liang; Chang, Ta-Yuan; Li, Bo-Liang#.RNA secondary structures located in the interchromosomal region of human ACAT1 chimeric mRNA are required to produce the 56-kDa isoform.CELL RESEARCH. 2008. 18(9):921-936.
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