孔娜
研究员
个人简介
研究员、博士生导师 浙江大学医学中心“计划”研究员 良渚实验室 课题组组长 浙江大学医学院附属第二医院 研究员 工作/学习经历 2022- 至今 浙江大学医学中心 研究员 2019-2022 哈佛大学医学院 博士后研究员 2017-2018 哈佛大学医学院 联合培养博士 主要研究方向为mRNA/cirRNA核酸治疗与智能新型生物材料。孔娜团队研发了国际领先且具有自主知识产权的“刺激-响应”mRNA递送平台,该递送平台能够精准靶向肿瘤组织并首次通过mRNA药物策略实现了抑癌因子p53的在肿瘤部位的活体修复,发挥高效肿瘤治疗和药物增敏效果,其相关研究成果发表在Science Translational Medicine期刊上(Sci. Transl. Med., 2019, 11(523), eaaw1565;获得F1000Prime高度推介并被评价为 Very Good;美国专利US20220016271A1)。孔娜团队还开发了世界首个粘性mRNA药物递送平台,能够实现mRNA药物的粘膜器官内局部递送,实现功能蛋白的特异性局部表达,用于疾病治疗临床转化或机理研究工作,其相关研究成果发表在《美国科学院院刊》期刊上(PNAS, 2022, 119(7) e2112696119;获得PNAS编辑部的高度推介且被选为正封面论文;受到《自然·医学》期刊编辑部的大篇幅亮点报道- Nat. Med., 2022, DOI 10.1038/s41591-022-01826-y - 一同接受采访的技术分别来自“mRNA疫苗全球顶级行业领导者”Moderna公司共同创始人/麻省理工学院Robert Langer院士团队、辉瑞制药研发副总裁Nicholas Warne博士团队、BioNTech药物递送技术副总裁Steffen Panzner博士团队、哈佛大学Samir Mitragotri院士团队等); 此外,基于孔娜团队在推动mRNA核酸治疗领域的发展以及mRNA技术的潜在临床应用方面做出的积极贡献,本团队还受邀在化学领域顶级综述期刊Chemical Society Reviews (影响因子54.564)上发表了题为“Emerging mRNA technologies delivery strategies and biomedical applications”的综述论文,重点介绍了mRNA递送策略及其生物应用研究,并展望了mRNA技术临床转化的进展和挑战,为mRNA技术今后进一步的发展指出了可能的方向(Chem. Soc. Rev., 2022, 51(10), 3828-3845;获得该期刊编辑部的高度推介,并被选为正封面论文)。 除了保证mRNA分子稳定性、安全性和有效性的设计、合成修饰,以及实现系统工业化生产的技术,孔娜团队还发明了其专有的mRNA环化技术平台并测试该平台可高效生产环形RNA(circRNA),这类circRNA分子能够稳定表达蛋白且其自身免疫源性较低。与线性mRNA相比,具有闭合环状结构的环状mRNA没有酶切的尾端,不易被核酸外切酶降解,结构更加稳定。环形RNA作为二代mRNA能够有效解决一代mRNA的局限性,其具有明显的优势以及产业化潜力。目前孔娜团队已申请/授权多项mRNA/cirRNA合成和递送系统相关发明专利、具有自主知识产权的mRNA修饰技术和递送技术,全方位解决了中国开发新型mRNA/cirRNA药物的“卡脖子”难题。目前,团队已与多家附属医院达成合作意向,共同开发应用于重大疾病的RNA药物。
研究领域
核酸药物 RNA治疗 生物材料 生物医学工程 药物递送
近期论文
After joining Zhejiang University as a PI · Liu C#, Shi Q#, Huang X, Koo S, Kong N*, Tao W*. mRNA-based cancer therapeutics. Nature Reviews Cancer 2023, 23(8): 526-543. (Highlighted in the "Nobel Prize in Physiology or Medicine 2023" Collection) · Ji X, Ge L, Liu C, Tang Z, Xiao Y, Chen W, Lei Z, Gao W, Blake S, De D, Shi B, Zeng X*, Kong N*, Zhang X*, Tao W*. Capturing functional two-dimensional nanosheets from sandwich-structure vermiculite for cancer theranostics. Nature Communications 2021, 12: 1124. (Web of Science Hot Paper | Highly Cited Paper; Highlighted: Nature Portfolio) · Shi Y#, Zhen X#, Zhang Y, Li Y, Koo S, Saiding Q, Kong N*, Liu G*, Chen W*, Tao W*. Chemically Modified Platforms for Better RNA Therapeutics. Chemical Reviews 2024, doi: 10.1021/acs.chemrev.3c00611. · Xiao Y, Tang Z, Huang X, Chen W, Zhou J, Liu H, Liu C, Kong N*, Tao W*. Emerging mRNA technologies: Delivery strategies and biomedical applications. Chemical Society Reviews 2022, 51(10): 3828-3845. (Front Cover Paper; Web of Science Highly Cited Paper) · Saiding Q#, Zhang Z#, Chen S, Xiao F, Chen Y, Li Y, Zhen X, Khan M, Chen W, Koo S*, Kong N*, Tao W*. Nano-bio interactions in mRNA nanomedicine: Challenges and opportunities for targeted mRNA delivery. Advanced Drug Delivery Reviews 2023, 203: 115116. (Invited Article) · Ouyang J, Rao S, Liu R, Wang L, Chen W, Tao W*, Kong N*. 2D Materials-based Nanomedicine: From Discovery to Applications. Advanced Drug Delivery Reviews 2022, 185: 114268. (Invited Article) · Jangili P, Kong N*, Kim JH, Zhou J, Liu H, Zhang X, Tao W*, Kim JS*. DNA-Damage-Response-Targeting Mitochondria-Activated Multifunctional Prodrug Strategy for Self-defensive Tumor Therapy. Angewandte Chemie International Edition 2022, 61(16): e202117075. (Angew. Chem. VIP; Front Cover Paper) First author publications at Harvard · Kong N, Tao W*, Ling X, Wang J, Xiao Y, Shi S, Ji X, Shajii A, Gan ST, Kim NY, Duda DG, Xie T*, Farokhzad OC*, Shi J*. Synthetic mRNA nanoparticle-mediated restoration of p53 tumor suppressor sensitizes p53-deficient cancers to mTOR inhibition. Science Translational Medicine 2019, 11(523): eaaw1565. Highlighted: F1000Prime Recommendation - Rated Very Good · Kong N, Zhang R, Wu G, Sui X*, Wang J, Kim NY, Blake S, De D, Xie T*, Cao Y, Tao W*. Intravesical Delivery of KDM6A-mRNA via Mucoadhesive Nanoparticles Inhibits the Metastasis of Bladder Cancer. Proceedings of the National Academy of Sciences USA 2022, 119(7): e2112696119 (PNAS Direct Submission). (Front Cover Paper; Web of Science Highly Cited Paper; Highlighted: Nature Medicine 2022, 28(6): 1100-1102) · Kong N, Zhang H, Feng C, Liu C, Xiao Y, Zhang X, Mei L, Kim JS, Tao W*, Ji X*. Arsenene-mediated multiple independently targeted reactive oxygen species burst for cancer therapy. Nature Communications 2021, 12: 4777. (Web of Science Hot Paper | Highly Cited Paper; Highlighted: Nature Portfolio) · Kong N, Ji X, Wang J, Sun X, Chen G, Fan T, Liang W, Zhang H, Xie A*, Farokhzad OC*, Tao W*. ROS-Mediated Selective Killing Effect of Black Phosphorus: Mechanistic Understanding and Its Guidance for Safe Biomedical Applications. Nano Letters 2020, 20(5): 3943-3955. (Web of Science Highly Cited Paper) · Huang X#, Kong N#(co-first), Zhang X#, Cao Y*, Langer R*, Tao W*. The landscape of mRNA nanomedicine. Nature Medicine 2022, 28(11): 2273–2287. (Featured article by Nature Medicine; Highlighted in the "Nobel Prize in Physiology or Medicine 2023" Collection; Web of Science Hot Paper | Highly Cited Paper) · Tang Z#, Kong N#(co-first), Zhang X#, Liu Y, Hu P, Mou S, Liljeström P, Shi J, Tan W, Kim JS, Cao Y, Langer R, Leong K, Farokhzad OC*, Tao W*. A materials science perspective on tackling COVID-19. Nature Reviews Materials 2020, 5(11): 847-860. (Front Cover Paper; Web of Science Highly Cited Paper; Highlighted: Nature Portfolio) · Tao W*#, Kong N#(co-first), Ji X#, Zhang Y, Sharma A, Ouyang J, Qi B, Wang J, Xie N, Kang C*, Zhang H*, Farokhzad OC, Kim JS*. Emerging two-dimensional Monoelemental materials (Xenes) for biomedical applications. Chemical Society Reviews 2019, 48(11): 2891-2912. (Front Cover Paper; Web of Science Hot Paper | Highly Cited Paper) · Zhu X#, Ji X#, Kong N#(co-first), Chen Y#, Mahmoudi M, Xu X, Ding L, Tao W*, Cai T, Li Y, Gan T, Barrett A, Bharwani Z, Chen H, Farokhzad OC*. Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis Enhanced Synergistic Cancer Therapy. ACS Nano 2018, 12(3): 2922–2938. (Web of Science Highly Cited Paper) · Ji X#, Kong N#(co-first), Wang J#, Li W, Xiao Y, Gan ST, Zhang Y, Li Y, Song X, Xiong Q, Shi S, Li Z, Tao W, Zhang H*, Mei L*, Shi J*. A Novel Top‐Down Synthesis of Ultrathin 2D Boron Nanosheets for Multimodal Imaging‐Guided Cancer Therapy. Advanced Materials 2018, 30(36): 1803031. (Cover Paper; Web of Science Highly Cited Paper)