课题组长期致力于基因治疗转化医学研究，在靶点发现、载体开发和临床转化方面均取得了突出贡献。代表性成果包括：1）开发了新型基因编辑递送载体——类病毒（VLP）载体；2）开发了树突状细胞靶向性VLP mRNA疫苗技术；3）首次发现神经元特有的抗病毒因子TMEFF1。VLP技术已用于多种疾病的基因编辑治疗临床研究，其中病毒性角膜炎的基因编辑治疗已进入临床二期。相关研究工作以最后通讯作者或共同通讯作者身份发表在 Nature、Nature Nanotechnology、Nature Biotechnology、Nature Biomedical Engineering、Cell Stem Cell 等学术期刊。研究成果入选“中国眼科学十大进展”与“中国血液领域十大医学研究”。此外，课题组长作为主要完成人获得国家科学技术进步奖一等奖和二等奖。课题组孵化了生物科技公司本导基因和锋寻生物。培养的多位博士研究生获得了国家奖学金、上海市优秀毕业生以及上海交通大学优秀博士论文奖。
课题组成员：乐黄莺 副研究员
助理研究员：刘小健
博士后：戴瑶
主要研究方向
1.发现：利用CRISPR全基因组文库、单细胞测序等系统性工具发现药物新靶点和生物学新机制。
2.发明：发明新型基因编辑工具、新型递送载体、新型免疫治疗技术，实现遗传疾病、肿瘤、病毒感染等难治性重大疾病的治疗。
3.应用：将原创性的发现和发明用于临床治疗，开发全球意义的first in class药物。
代表性成果
1. Y. Dai, M. Idorn, M. C. Serrero, X. Pan, E. A. Thomsen, R. Narita, M. Maimaitili, X. Qian, M. B. Iversen, L. S. Reinert, R. K. Flygaard, M. Chen, X. Ding, B.-c. Zhang, M. E. Carter-Timofte, Q. Lu, Z. Jiang, Y. Zhong, S. Zhang, L. Da, J. Zhu, M. Denham, P. Nissen, T. H. Mogensen, J. G. Mikkelsen, S.-Y. Zhang, J.-L. Casanova, Y. Cai#, S. R. Paludan#, TMEFF1 is a neuron-specific restriction factor for herpes simplex virus. Nature, 632, 383-389 (2024).
2. S. Ling, X. Zhang, Y. Dai, Z. Jiang, X. Zhou, S. Lu, X. Qian, J. Liu, N. Selfjord, T.M. Satir, A. Lundin, J.L. Touza, M. Firth, N. Van Zuydam, B. Bilican, P. Akcakaya, J. Hong# & Y. Cai#. Customizable virus-like particles deliver CRISPR-Cas9 ribonucleoprotein for effective ocular neovascular and Huntington's disease gene therapy. Nature Nanotechnology, 20, 543-553 (2025). (高被引论文)
3. D. Yin, Y. Zhong, S. Ling, S. Lu, X. Wang, Z. Jiang, J. Wang, Y. Dai, X. Tian, Q. Huang, X. Wang, J. Chen, Z. Li, Y. Li, Z. Xu, H. Jiang, Y. Wu, Y. Shi, Q. Wang, J. Xu, W. Hong, H. Xue, H. Yang, Y. Zhang, L. Da, Z.-g. Han, S.-c. Tao, R. Dong, T. Ying, J. Hong#, Y. Cai#, Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers. Nature Biomedical Engineering, 9, 185-200, (2025). (高被引论文)
4. S. Li, S. Ling, D. Wang, X. Wang, F. Hao, L. Yin, Z. Yuan, L. Liu, L. Zhang, Y. Li, Y. Chen, L. Luo, Y. Dai, L. Zhang, L. Chen, D. Deng, W. Tang, S. Zhang, S. Wang#, Y. Cai#. Modified lentiviral globin gene therapy for pediatric β0/β0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial. Cell Stem Cell, 31, 961-973.e968 (2024). (高被引论文)
5. Y. Zhong, H. Le, X. Zhang, Y. Dai, F. Guo, X. Ran, G. Hu, Q. Xie, D. Wang#, Y. Cai#, Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening. Journal of Hematology & Oncology 17, 36 (2024).
6. D. Yin, S. Ling, D. Wang, Y. Dai, H. Jiang, X. Zhou, S. R. Paludan, J. Hong#, Y. Cai#, Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice. Nature Biotechnology, 39, 567-577 (2021). (高被引论文)
7. S. Ling, S. Yang, X. Hu, D. Yin, Y. Dai, X. Qian, D. Wang, X. Pan, J. Hong, X. Sun, H. Yang, S. R. Paludan, Y. Cai#, Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice. Nature Biomedical Engineering, 5, 144-156 (2021). (高被引论文)
8. A. Wei, D. Yin, Z. Zhai, S. Ling, H. Le, L. Tian, J. Xu, S. R. Paludan, Y. Cai#, J. Hong#, In vivo CRISPR gene editing in patients with herpetic stromal keratitis. Molecular Therapy 31, 3163-3175 (2023).
9. S. Lu, Y. Cai#, Bacterial molecular syringe for drug delivery. Cell Host Microbe, 31, 917-919 (2023).
10. C. Guo, Z. Long, P. Lin, Y. Shen, Y. Zhong, J. Qian, J. Yu, W. Zhao, F. Liu, Y. Ma, J. Zheng, J. Yang, S. Zhao, X. Ran, Z. Xia, C. Wu, Y. Cai#, C. Wang# & Q. Xie#. BRD9 inhibition overcomes oncolytic virus therapy resistance in glioblastoma. Cell Rep Med, 6, 102258 (2025).
