Group of DNA Repair, Gene Editing & Gene Therapy
Jia ChenAssociate Professor , PhD, Associate Professor
School of Life Science and Technology
- 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
- 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)
DNA Repair, Gene Editing and Gene Therapy
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.
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.