Research Focus

Life follows the central dogma of DNA to protein, where this intricate "source code" and the environment together define an organism's form and function. Gene editing technology, acting as a "scalpel" capable of directly rewriting this source code, has revolutionarily reshaped modern life sciences. The Yi Laboratory stands at the forefront of this transformation, dedicated to integrating cutting-edge interdisciplinary approaches like artificial intelligence and protein engineering to create novel gene editing and drug delivery systems. Our core objective is to develop precise, efficient, and safe therapeutic tools to fundamentally address major human ailments such as genetic diseases and cancer. We are committed to a full-chain research paradigm—"from tool creation to disease solution"—and encourage team members to wield advanced technologies as the spear and clinical challenges as the shield, seeking original breakthroughs through interdisciplinary exploration.

1.AI-Driven Development of Novel Gene Editing Tools: We utilize artificial intelligence algorithms and high-throughput protein engineering to design and build gene editors with novel functions, enhanced precision, and improved safety. Concurrently, we advance the establishment and optimization of high-throughput protein engineering platforms.

2.Delivery Technology Development: Focusing on the key bottleneck in gene therapy—delivery systems—we aim to engineer virus-like particles that combine the efficient targeting of viral vectors with the safety profile of non-viral vectors, paving new paths for the precise in vivo delivery of therapeutic macromolecules. We also explore novel methods and technologies for delivering drugs precisely to subcellular organelles.

3.Disease Mechanism Investigation and Precision Therapy Based on Cutting-Edge Technologies: We apply our self-developed gene editing tools and delivery platforms directly in disease model studies. A current priority is tackling refractory diseases like mitochondrial genetic disorders. Through precise repair or introduction of specific genetic variations, we aim to deeply elucidate disease mechanisms and develop tangible, effective treatment strategies.

Research Achievements

1.Developed a nickase-based mitochondrial DNA base editor, enabling strand-selective, highly efficient, and precise mitochondrial base editing (Nature Biotechnology, 2023). Further optimization of this technology facilitated the creation of a series of mouse models harboring mitochondrial mutations, such as for Leigh syndrome and LHON, addressing the longstanding gap in animal models for mitochondrial diseases (Nature, 2025).

2.Developed LEAPER, a technology leveraging endogenous cellular ADAR proteins for highly precise RNA base editing with low off-target effects (Nature Biotechnology, 2019). Subsequently, utilized engineered circular RNA to achieve RNA single-base editing (Nature Biotechnology, 2022), successfully treating a humanized Hurler syndrome mouse model and demonstrating application in a non-human primate model (Genome Biology, 2023).

3.Developed the world's first circular RNA vaccine platform, creating vaccines against SARS-CoV-2 variants that showed promising protective efficacy in non-human primates (Cell, 2022).

Representative Publications

*Co-first author

^#Co-corresponding author

1.X. Zhang, X. Zhang, J. Ren, J. Li, X. Wei, Y Yu, Z. Yi^#, W. Wei^#, Precise modelling of mitochondrial diseases using optimized mitoBEs. Nature (2025).

2.Z. Yi*, X. Zhang*, X. Wei*, J. Li*, J. Ren, X. Zhang, Y. Zhang, H. Tang, X. Chang, Y. Yu, W. Wei^#, Programmable DNA pyrimidine base editing via engineered uracil-DNA glycosylase. Nature Communications (2024).

3.X. Zhang*, Z. Yi*, W. Tang, W. Wei^#, Streamlined process for effective and strand-selective mitochondrial base editing using mitoBEs. Biophysics Reports (2024).

4.Z. Yi*, Y. Zhao*, Z. Yi*, Y. Zhang*, G. Tang, X. Zhang, H. Tang, W. Zhang, Y. Zhao, H. Xu, Y. Nie, X. Sun, L. Xing, L. Dai, P. Yuan^#, W. Wei^#, Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice. Genome Biology (2023).

5.Z. Yi*, X. Zhang*, W. Tang, Ying. Yu, X. Wei, X. Zhang, W. Wei^#, Strand-selective base editing of human mitochondrial DNA using mitoBEs. Nature Biotechnology (2023).

6.Z. Yi*, L. Qu*, H. Tang*, Z. Liu, Y. Liu, F. Tian, C. Wang, X. Zhang, Z. Feng, Y. Yu, P. Yuan, Z. Yi, Y. Zhao, W. Wei^#, Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo. Nature Biotechnology (2022).

Research Highlight: In vivo RNA base editing with circular RNAs. Nature Reviews Genetics (2022).

7.L. Qu*, Z. Yi*, Y. Shen*, L. Lin, F. Chen, Y. Xu, Z. Wu, H. Tang, X. Zhang, F. Tian, C. Wang, X. Xiao, X. Dong, L. Guo, S. Lu, C. Yang, C. Tang, Y. Yang, W. Yu, J. Wang, Y. Zhou, Q. Huang, A. Yisimayi, Y. Cao, Y. Wang, Z. Zhou, X. Peng, J. Wang, X. S. Xie, W. Wei^#, Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants. Cell (2022).

8.L. Qu*, Z. Yi*, S. Zhu*, C. Wang*, Z. Cao*, Z. Zhou*, P. Yuan*, Y. Yu, F. Tian, Z. Liu, Y. Bao, Y. Zhao, W. Wei^#, Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nature Biotechnology (2019).

Research Highlight: Expanding the RNA-editing toolbox. Nature Reviews Drug Discovery (2019).

Research Highlight: Expanding options for RNA based editors. Nature Reviews Genetics (2019).