文献类型：期刊文献

英文题名：Rational Design of Polymeric mRNA Delivery Vectors to Achieve Excellent Room-Temperature Storage Stability and Delivery Efficiency

作者：Shi, Junqiu[1];Yin, Haiyang[1];Sun, Qingmei[1];Teng, Runxin[1];Zhu, Yunqing[1];Du, Jianzhong[2,3,4]

机构：[1]Tongji Univ, Sch Mat Sci & Engn, Dept Polymer Mat, Shanghai 201804, Peoples R China;[2]Tongji Univ, Shanghai Peoples Hosp 4, Translat Res Inst Brain & Brain Like Intelligence, Sch Med,Clin Res Ctr Anesthesiol & Perioperat Med,, Shanghai 200434, Peoples R China;[3]Tongji Univ, Sch Mat Sci & Engn, Key Lab Adv Civil Engn Mat, Minist Educ, Shanghai 201804, Peoples R China;[4]East China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China

年份：2024

卷号：36

期号：11

起止页码：5422

外文期刊名：CHEMISTRY OF MATERIALS

收录：;EI(收录号：20242116118092);WOS:【SCI-EXPANDED(收录号:WOS:001226103300001)】；

基金：This project is supported by National Key R&D Program of China (2022YFC2402900), National Natural Science Foundation of China (21925505, 22335005, 22175131), Innovation Program of Shanghai Municipal Education Commission (2023ZKZD28), the International Scientific Collaboration Fund of Science and Technology Commission of Shanghai Municipality (21520710100), and the Interdisciplinary Collaborative Research Project (Grant No. 2023-2-YB-03).

语种：英文

外文关键词：Amines - Cells - Cytology - Room temperature - Stability - Vectors

摘要：Delivery vectors play an important role in delivering mRNA. However, it is an important challenge to enhance room-temperature storage stability and balance the conflicting requirements for excellent in vivo stability and mRNA release performance. In response to the above problems, we propose a "4Q" principle for designing mRNA delivery vectors. The overall delivery efficiency (Q) of mRNA is related to the stability of the delivery vector itself (Q S , including storage stability and in vivo stability which was rarely considered previously), the performance of diffusion to the target cells (Q D ), the ability to enter the cytoplasm through the cell membrane (Q I ), and the performance of the intracellular release of mRNA (Q R ). The efficiencies of each step are crucial to high overall delivery efficiency of intramuscular injection. Based on this "4Q" principle, we designed a new cationic polycatechol, poly(N,N '-bis(acryloyl)cystamine-co-dopamine) (PBD). The PBD/mRNA polyplexes are stable at room temperature for more than 2 weeks (Q S up arrow). The in vivo transfection fluorescence intensity of polyplexes was 2 orders of magnitude higher than the commercially available mRNA delivery system (e.g., jetPEI/mRNA). Overall, this new "4Q" principle will be helpful for designing clinically transformative mRNA vectors with excellent storage stability and delivery efficiency.