At Penn

* Corresponding author † Equal contribution

40. Directed evolution expands CRISPR-Cas12a gene targeting capacity. Enbo Ma†, Kai Chen†, Honglue Shi†, Kevin M. Wasko, Isabel Esain-Garcia, Marena I. Trinidad, Kaihong Zhou, Jinjuan Ye, Jennifer A. Doudna*. Nucleic Acids Res. 53, gkaf649 (2025).

39. Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 ribonucleoprotein. Kai Chen†, Hesong Han†, Sheng Zhao, Bryant Xu, Boyan Yin, Atip Lawanprasert, Marena Trinidad, Benjamin W. Burgstone, Niren Murthy*, Jennifer A. Doudna*. Nat. Biotech. 43, 1445–1457 (2025).

38. Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9. Amy R. Eggers†, Kai Chen†, Katarzyna M. Soczek, Owen T. Tuck, Erin E. Doherty, Bryant Xu, Marena I. Trinidad, Brittney W. Thornton, Peter H. Yoon, Jennifer A. Doudna*. Cell 187, 3249–3261 (2024).

37. Engineering self-deliverable ribonucleoproteins for genome editing in the brain. Kai Chen†, Elizabeth C. Stahl†, Min Hyung Kang, Bryant Xu, Ryan Allen, Marena Trinidad, Jennifer A. Doudna*. Nat. Comm. 15, 1724 (2024).

36. Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes. Peter H. Yoon, Petr Skopintsev, Honglue Shi, LinXing Chen, Benjamin A. Adler, Muntathar Al-Shimary, Rory J. Craig, Kenneth J. Loi, Evan C. DeTurk, Zheng Li, Jasmine Amerasekera, Marena Trinidad, Hunter Nisonoff, Kai Chen, Arushi Lahiri, Ron Boger, Steve Jacobsen, Jillian F. Banfield, Jennifer A. Doudna*. Nucleic Acids Res. 51, 12414–12427 (2023).

35. Improved genome editing by an engineered CRISPR-Cas12a. Enbo Ma†, Kai Chen†, Honglue Shi, Elizabeth C. Stahl, Ben Adler, Marena Trinidad, Junjie Liu, Kaihong Zhou, Jinjuan Ye, Jennifer A. Doudna*. Nucleic Acids Res. 50, 12689–12701 (2022).

34. Enzymatic assembly of diverse lactone structures: An intramolecular C–H functionalization strategy. Daniel J. Wackelin, Runze Mao, Kathleen M. Sicinski, Yutao Zhao, Anuvab Das, Kai Chen*, Frances H. Arnold*. J. Am. Chem. Soc. 146, 1580–1587 (2024).

33. Reversing the enantioselectivity of enzymatic carbene N–H insertion through mechanism-guided protein engineering. Carla Calvó-Tusell, Zhen Liu*, Kai Chen, Frances H. Arnold, Marc Garcia-Borràs*. Angew. Chem. Int. Ed. e202303879 (2023).

32. Chapter 4: Engineering enzymes for new-to-nature carbene chemistry. Soumitra V. Athavale, Kai Chen, Frances H. Arnold*. Book chapter in “Transition Metal-Catalyzed Carbene Transformations” (edited by Jianbo Wang, Chi-Ming Che, Michael P. Doyle), WILEY-VCH GmbH (2022).

31. Dual-function enzyme catalysis for enantioselective carbon–nitrogen bond formation. Zhen Liu, Carla Calvó-Tusell, Andrew Z. Zhou, Kai Chen*, Marc Garcia-Borràs*, Frances H. Arnold*. Nat. Chem. 13, 1166–1172 (2021).

30. Enzymatic lactone-carbene C‒H insertion to build contiguous chiral centers. Andrew Z. Zhou, Kai Chen*, Frances H. Arnold*. ACS Catal. 10, 5393–5398 (2020).

29. Engineering cytochrome P450s for enantioselective cyclopropenation of internal alkynes. Kai Chen, Frances H. Arnold*. J. Am. Chem. Soc. 142, 6891–6895 (2020).

28. Engineering new catalytic activities in enzymes. Kai Chen, Frances H. Arnold*. Nat. Catal. 3, 103–113 (2020).

27. Directed evolution of a cytochrome P450 carbene transferase for selective functionalization of cyclic compounds. Oliver F. Brandenberg, Kai Chen, Frances H. Arnold*. J. Am. Chem. Soc. 141, 8989–8995 (2019).

26. Engineered cytochrome c-catalyzed lactone-carbene B–H insertion. Kai Chen, Xiongyi Huang, Shuo-Qing Zhang, Andrew Z. Zhou, S. B. Jennifer Kan, Xin Hong*, Frances H. Arnold*. Synlett 30, 378–382 (2019) in the 30 Years SYNLETT – Pearl Anniversary Issue.

25. Enzymatic assembly of carbon–carbon bonds via iron-catalysed sp3C–H functionalization. Ruijie K. Zhang, Kai Chen, Xiongyi Huang, Lena Wohlschlager, Hans Renata, Frances H. Arnold*. Nature 565, 67–72 (2019).

24. Alternate heme ligation steers activity and selectivity in engineered cytochrome P450-catalyzed carbene transfer reactions. Kai Chen†, Shuo-Qing Zhang†, Oliver F. Brandenberg, Xin Hong*, Frances H. Arnold*. J. Am. Chem. Soc. 140, 16402–16407 (2018).

23. Enzymatic construction of highly strained carbocycles. Kai Chen, Xiongyi Huang, S. B. Jennifer Kan, Ruijie K. Zhang, Frances H. Arnold*. Science 360, 71–75 (2018).

22. Stereoselective enzymatic synthesis of heteroatom-substituted cyclopropanes. Oliver F. Brandenberg, Christopher K. Prier, Kai Chen, Anders M. Knight, Zachary Wu, Frances H. Arnold*. ACS Catal. 8, 2629–2634 (2018).

21. Diverse engineered heme proteins enable stereodivergent cyclopropanation of unactivated alkenes. Anders M. Knight, S. B. Jennifer Kan, Russell D. Lewis, Oliver F. Brandenberg, Kai Chen, Frances H. Arnold*. ACS Cent. Sci. 4, 372–377 (2018).

20. Genetically programmed chiral organoborane synthesis. S. B. Jennifer Kan, Xiongyi Huang, Yosephine Gumulya, Kai Chen, Frances H. Arnold*. Nature 552, 132–136 (2017).

19. Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life. S. B. Jennifer Kan, Russell D. Lewis, Kai Chen, Frances H. Arnold*. Science 354, 1048–1051 (2016).

18. Macrocyclic peptide construction through C–H activation strategy. Kai Chen, Bing-Feng Shi*. Sci. Bull. 68, 1238–1240 (2018).

17. Palladium-catalyzed sequential monoarylation/amidation of C(sp3)–H bonds: Stereoselective synthesis of α-amino-β-lactams and anti-α,β-diamino acid. Peng-Xiang Ling, Sheng-Long Fang, Xue-Song Yin, Qi Zhang, Kai Chen, Bing-Feng Shi*. Chem. Comm. 53, 6351–6354 (2017).

16. Palladium-catalyzed interannular meta-C–H arylation. Peng-Xiang Ling, Kai Chen, Bing-Feng Shi*. Chem. Comm. 53, 2166–2169 (2017).

15. Divergent and stereoselective synthesis of β-silyl-α-amino acids through palladium-catalyzed intermolecular silylation of unactivated primary and secondary C–H bonds. Yue-Jin Liu, Yan-Hua Liu, Zhuo-Zhuo Zhang, Sheng-Yi Yan, Kai Chen, Bing-Feng Shi*. Angew. Chem. Int. Ed. 55, 13859–13862 (2016).

14. Stereoselective alkoxycarbonylation of unactivated C(sp3)–H bonds with alkyl chloroformates via Pd (II)/Pd (IV) catalysis. Gang Liao, Xue-Song Yin, Kai Chen, Qi Zhang, Shuo-Qing Zhang, Bing-Feng Shi*. Nat. Comm. 7, 12901 (2016).

13. Palladium-catalyzed C(sp3)–H arylation of lactic acid: Efficient synthesis of chiral β-aryl-α-hydroxy acids. Kai Chen†, Xin Li†, Shuo-Qing Zhang, Bing-Feng Shi*. Org. Chem. Front. 3, 204–208 (2016).

12. Synthesis of chiral α-hydroxy acids via palladium-catalyzed C(sp3)–H alkylation of lactic acid. Kai Chen†, Xin Li†, Shuo-Qing Zhang, Bing-Feng Shi*. Chem. Comm. 52, 1915–1918 (2016).

11. Palladium-catalyzed arylation of unactivated γ-methylene C(sp3)–H and δ-C–H bonds with an oxazoline-carboxylate auxiliary. Peng-Xiang Ling, Sheng-Long Fang, Xue-Song Yin, Kai Chen, Bo-Zheng Sun, Bing-Feng Shi*. Chem-Eur. J. 21, 17503–17507 (2015).

10. Pd(II)-catalyzed direct sulfonylation of unactivated C(sp3)‒H bonds with sodium sulfinates. Wei-Hao Rao, Bei-Bei Zhan, Kai Chen, Peng-Xiang Ling, Zhuo-Zhuo Zhang, Bing-Feng Shi*. Org. Lett. 17, 3552–3555 (2015).

9. Stereoselective synthesis of chiral β-fluoro-α-amino acids via Pd(II)-catalyzed fluorination of unactivated methylene C(sp3)‒H bonds: Scope and mechanistic studies. Qi Zhang, Xue-Song Yin, Kai Chen, Shuo-Qing Zhang, Bing-Feng Shi*. J. Am. Chem. Soc. 137, 8219–8226 (2015).

8. Practical synthesis of anti-β-hydroxy-α-amino acids via Pd(II)-catalyzed sequential C(sp3)–H functionalization. Kai Chen, Shuo-Qing Zhang, Huai-Zhi Jiang, Jing-Wen Xu, Bing-Feng Shi*. Chem-Eur. J. 21, 3264–3270 (2015).

7. A general and practical palladium-catalyzed monoarylation of β-methyl C(sp3)–H of alanine. Kai Chen, Shuo-Qing Zhang, Jing-Wen Xu, Fang Hu, Bing-Feng Shi*. Chem. Comm. 50, 13924–13927 (2014).

6. Sulfonamide-promoted palladium(II)-catalyzed alkylation of unactivated methylene C(sp3)–H bonds with alkyl iodides. Kai Chen, Bing-Feng Shi*. Angew. Chem. Int. Ed. 53, 11950–11954 (2014).

5. Recent progress in the synthesis of functionalized β-lactams via transition-metal-catalyzed C(sp3)–H amidation. Qi Zhang, Kai Chen, Bing-Feng Shi*. Synlett. 25, 1941–1945 (2014).

4. Stereoselective synthesis of chiral α-amino-β-lactams via Pd(II)-catalyzed sequential monoarylation/amidation of C(sp3)–H bonds. Qi Zhang, Kai Chen, Weihao Rao, Yuejun Zhang, Fa-Jie Chen, Bing-Feng Shi*. Angew. Chem. Int. Ed. 52, 13588–13592 (2013).

3. Pd(II)-catalyzed alkoxylation of unactivated C(sp3)–H and C(sp2)–H bonds using a removable directing group: Efficient synthesis of alkyl ethers. Fa-Jie Chen, Sheng Zhao, Fang Hu, Kai Chen, Qi Zhang, Shuo-Qing Zhang, Bing-Feng Shi*. Chem. Sci. 4, 4187–4192 (2013).

2. Pd(II)-catalyzed alkylation of unactivated C(sp3)–H bonds: Efficient synthesis of optically active unnatural α-amino acids. Kai Chen, Fang Hu, Shuo-Qing Zhang, Bing-Feng Shi*. Chem. Sci. 4, 3906–3911 (2013).

1. Synthesis of benzoxazine and 1,3-oxazine derivatives via ligand-free copper(I)-catalyzed one-pot cascade addition/cyclization reaction. Guodong Shen, Dingben Chen, Yiliang Zhang, Manman Sun, Kai Chen, Cong Jin, Kaining Li, Weiliang Bao*. Tetrahedron 68, 166–172 (2012).