Base Editing

Base Editing

Base editing technology induces precise base substitutions to achieve genome editing through combining two moieties, "effector" and "locator".


CRISPR-mediated Gene Editing and Base Editing

More than 75,000 genetic mutations are corelated with human diseases and around half of these diseases are caused by point mutations, which are hard to be fixed by traditional gene editing tools. Base editing technology can realize single base pair change in human genome in a precise and permanent manner. Thus, base editing technology provides great potential for the cure of hereditary diseases and the immunotherapy of cancer.


Our Technology

Our Base Editing Systems

Our scientific founders have developed five series base editing systems, including enhanced Base Editor (eBE), dCpf1 Base Editor (dCpf1-BE), human APOBEC3A Base Editor (hA3A-BE), BEACON, transformer Base Editor (tBE).

transformer Base Editor (tBE) with Ultra-high Editing Precision

tBE was developed with ultra-high editing precision to eliminate both gRNA-dependent and gRNA-independent off-target mutations (tBE, Nature Cell Biology, 2021). Through a cleavable “lock”, tBE becomes active only at on-target sites to induce highly efficient editing. When binding at off-target sites, tBE was “locked” to avoid triggering off-target mutations. Like a “Transformer”, tBE has great flexibility to suit for different kinds of deliver methods such as AAV and mRNA/LNP. Furthermore, tBE can simultaneously edit multiple target sites with high efficiency. These characters greatly expand the scope of tBE’s clinical application. 


▲ transformer Base Editor (tBE) of Correctseq

(Han et al., Nature Protocols, 2023)

Gene Therapy

Base Editing Therapy

With traditional transgene therapy, the original mutations still exist, which makes it hard to be applied to treat the hereditary diseases caused by dominant-negative mutations. Also, the lifelong effect of transgene therapy is yet to be validated. Comparing with transgene therapy, base editing therapy which can be applied in vivo and ex vivo fixes the mutations directly and can cure various genetic diseases for a lifelong effect. Compared with Cas Nuclease gene editing therapy, tBE exhibits undetected off-target mutations, higher editing efficiency and better therapeutic effect, and lower cytotoxicity.


Scientific Publications

  Research Articles
  Reviews, Comments, Interviews

1. Li X#*, Zhou L#, Gao BQ#, Li G, Wang X, Wang Y, Wei J, Han W, Wang Z, Li J, Gao R, Zhu J, Xu W, Wu J, Yang B, Sun X*, Yang L*, Chen J*. 2022. Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure. Nat Commun, 13(1):1669.

2. Gao R#, Fu ZC#, Li X#, Wang Y#, Wei J, Li G, Wang L, Wu J, Huang X*, Yang L*, Chen J*. 2022. Genomic and Transcriptomic Analyses of Prime Editing Guide RNA-Independent Off-Target Effects by Prime Editors. CRISPR J, 5(2):276-293.

3. Wang J#, He Z#, Wang G#, Zhang R#, Duan J, Gao P, Lei X, Qiu H, Zhang C, Zhang Y, Yin H*. 2022. Efficient targeted insertion of large DNA fragments without DNA donors. Nat Methods, 19(3): 331-340.

4. Gao X#, Ma XK#, Li X, Li GW, Liu CX, Zhang J, Wang Y, Wei J, Chen J, Chen LL and Yang L*. 2022. Knockout of circRNAs by base editing back-splice sites of circularized exons. Genome Biol, 23: 16.

5. Wang L#, Xue W#, Zhang H#, Gao R#, Qiu H#, Wei J, Zhou L, Lei YN, Wu X, Li X, Liu C, Wu J, Chen Q, Ma H, Huang X, Cai C, Zhang Y, Yang B*, Yin H*, Yang L* and Chen J*. 2021. Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations. Nat Cell Biol, 23(5): 552-563.

6. Wang X#, Ding C#, Yu W#, Wang Y#, He S#, Yang B#, Xiong YC, Wei J, Li J, Liang J, Lu Z, Zhu W, Wu J, Zhou Z, Huang X, Liu Z*, Yang L* and Chen J*. 2020. Cas12a Base Editors Induce Efficient and Specific Editing with Low DNA Damage Response. Cell Rep, 31(9): 107723.

7. Song CQ#, Jiang T#, Richter M, Rhym LH, Koblan LW, Zafra MP, Schatoff EM, Doman JL, Cao Y, Dow LE, Zhu LJ, Anderson DG, Liu DR*, Yin H*, and Xue W*. 2020. Adenine base editing in an adult mouse model of tyrosinaemia. Nat Biomed Eng, 4: 125-130.

8. Wang Y#, Gao R#, Wu J#, Xiong YC, Wei J, Zhang S, Yang B, Chen J* and Yang Y*. 2019. Comparison of cytosine base editors and development of the BEable-GPS database for targeting pathogenic SNVs. Genome Biol, 20(1): 218.

9. Wang X#, Li J#, Wang Y#, Yang B#, Wei J#, Wu J, Wang R, Huang X*, Chen J* and Yang L*. 2018. Efficient base editing in methylated regions with a human APOBEC3A-Cas9 fusion. Nat Biotechnol, 36(10): 946-949.

10. Li X#, Wang Y#, Liu Y#, Yang B#, Wang X, Wei J, Lu Z, Zhang Y, Wu J, Huang X*, Yang L* and Chen J*. 2018. Base editing with a Cpf1-cytidine deaminase fusion. Nat Biotechnol, 36(4): 324-327.

11. Xiang JF#, Yang Q#, Liu CX#, Wu M, Chen LL* and Yang L*. 2018. N(6)-Methyladenosines Modulate A-to-I RNA Editing. Mol Cell, 69(1): 126-135 e126.

12. Lei L#, Chen H#, Xue W#, Yang B#, Hu B#, Wei J, Wang L, Cui Y, Li W, Wang J, Yan L, Shang W, Gao J, Sha J, Zhuang M, Huang X, Shen B*, Yang L* and Chen J*. 2018. APOBEC3 induces mutations during repair of CRISPR-Cas9-generated DNA breaks. Nat Struct Mol Biol, 25(1): 45-52.

13. Yin H#, Song CQ#, Suresh S, Kwan SY, Wu Q, Walsh S, Ding J, Bogorad RL, Zhu LJ, Wolfe SA, Koteliansky V, Xue W*, Langer R* and Anderson DG*. 2018. Partial DNA-guided Cas9 enables genome editing with reduced off-target activity. Nat Chem Biol, 14(3):311-316.

14. Wang L#, Xue W#, Yan L#, Li X, Wei J, Chen M, Wu J, Yang B*, Yang L* and Chen J*. 2017. Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor. Cell Res, 27(10): 1289-1292.

15. Yin H, Song CQ, Suresh S, Wu Q, Walsh S, Rhym LH, Mintzer E, Bolukbasi MF, Zhu LJ, Kauffman K, Mou H, Oberholzer A, Ding J, Kwan SY, Bogorad RL, Zatsepin T, Koteliansky V, Wolfe SA, Xue W, Langer R and Anderson DG*. 2017. Structure-guided chemical modification of guide RNA enables potent non-viral in vivo genome editing. Nat Biotechnol, 35(12):1179-1187.

16. Yin H, Song CQ, Dorkin JR, Zhu L, Li Y, Wu Q, Park A, Yang J, Suresh S, Bizhanova A, Gupta A, Bolukbasi M, Walsh S, Bogorad R, Gao G, Weng Z, Dong Y, Koteliansky V, Wolfe S, Langer R, Xue W* and Anderson DG*. 2016. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol, 34(3):328-33.

17. Zhang XO#, Wang HB#, Zhang Y, Lu X, Chen LL* and Yang L*. 2014. Complementary sequence-mediated exon circularization. Cell, 159(1): 134-147.

18. Yin H#, Xue W#, Chen S, Bogorad RL, Benedetti E, Grompe M, Koteliansky V, Sharp PA, Jacks T and Anderson DG*. 2014. Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype. Nat Biotechnol, 32(6): 551-553.

19. Xue W#, Chen S#, Yin H#, Tammela T, Papagiannakopoulos T, Joshi NS, Cai W, Yang G, Bronson R, Crowley DG, Zhang F, Anderson DG, Sharp PA and Jacks T*. 2014. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature, 514(7522): 380-384.

20. Chen J, Miller BF and Furano AV*. 2014. Repair of naturally occurring mismatches can induce mutations in flanking DNA. Elife, 3: e02001.

1. Gao C* and Chen J*. 2021. CRISPR Adventures in China. CRISPR J, 4(3): 304-306.

2. Chen Q, Zhang Y* and Yin H*. 2021. Recent advances in chemical modifications of guide RNA, mRNA and donor template for CRISPR-mediated genome editing. Adv Drug Deliv Rev, 168: 246–258.

3. Yang L* and Chen J*. 2020. A Tale of Two Moieties: Rapidly Evolving CRISPR/Cas-Based Genome Editing. Trends Biochem Sci, 45(10): 874-888.

4. Yang L*, Yang B* and Chen J*. 2019. One Prime for All Editing. Cell, 179(7): 1448-1450.

5. Chen J*, Yang B* and Yang L*. 2019. To BE or not to BE, that is the question. Nature Biotechnology, 37(5): 520-522.

6. Yang B*, Yang L* and Chen J*. 2019. Development and Application of Base Editors. CRISPR J, 2(2): 91-104.

7. Zhang HX, Zhang Y* and Yin H*. 2019. Genome Editing with mRNA Encoding ZFN, TALEN, and Cas9. Mol Ther, 27(4): 735–746.

8. Yin H*, Xue W* and Anderson DG*. 2019. CRISPR-Cas: a tool for cancer research and therapeutics. Nat Rev Clin Oncol, 16(5): 281-295.

9. Pawluk A*, Chen J, Ji W and Mali P. 2018. The Future of Genome Editing. Cell, 173(6): 1311-1313.

10. Yang B*, Li X, Lei L and Chen J*. 2017. APOBEC: From mutator to editor. J Genet Genomics, 44(9): 423-437.

11. Yin H, Kauffman KJ and Anderson DG*. 2017. Delivery technologies for genome editing. Nat Rev Drug Discov, 16(6): 387-399.

12. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR and Anderson DG*. 2014. Non-viral vectors for gene-based therapy. Nat Rev Genet, 15(8): 541-555.

(#: co-first author, *: corresponding author)

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