文献类型：期刊文献

英文题名：One-component ionizable amphiphilic Janus dendrimers as a delivery platform for efficient mRNA vaccine development

作者：Ona, Nathan A.[1,2];Zhang, Dapeng[3];Lindesmith, Lisa C.[4];Park, Wook-Jin[1,2];Meshanni, Jaclynn A.[1,2];Berkihiser, Sydni[1,2];Vasserman, Jessica A.[1];Toshtzar, Sepideh[1];Moore, Nathanael C.[1];Williams, Blair[1];Nakagawa, Benjamin[1];Baboo, Ishana[1];Pan, Liuyan[3];Cheng, Wanting[3];Mercado-Lopez, Xiomara[1,2];Bonilla-Acosta, Wendy[2];Brewer-Jensen, Paul D.[4];Zweigart, Mark R.[4];Reyes, Yaoska I.[4];Mallory, Michael L.[4];May, Samantha R.[4];Zhou, Yongfeng[5];Percec, Virgil[6];Baric, Ralph S.[4];Li, Yongsheng[3];Weissman, Drew[1,2];Atochina-Vasserman, Elena N.[1,2]

机构：[1]Univ Penn, Perelman Sch Med, Penn Inst RNA Innovat, Philadelphia, PA 19104 USA;[2]Univ Penn, Perelman Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA;[3]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai, Peoples R China;[4]Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA;[5]Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Frontiers Sci Ctr Transformat Mol, Shanghai, Peoples R China;[6]Univ Penn, Dept Chem, Roy & Diana Vagelos Labs, Philadelphia, PA USA

年份：2026

卷号：12

期号：13

外文期刊名：SCIENCE ADVANCES

收录：;EI(收录号：20262020698316);WOS:【SCI-EXPANDED(收录号:WOS:001727101900006)】；

基金：This work was supported by NIH R01 AI148260 and AI158571 (R.S.B.) and NSF DMR-2104554 and DMR-1720530 (V.P.).This work was partially supported by the Wellcome Leap R3 program (V.P. and D.W.).

语种：英文

外文关键词：Cell membranes - Cost effectiveness - Diseases - RNA

摘要：There have been rapid advances in nucleoside-modified messenger RNA-based vaccines, particularly during the SARS-CoV-2 pandemic, demonstrating a rapid and cost-effective approach for addressing infectious diseases. A major challenge remains in developing a delivery system that protects mRNA from degradation and facilitates its passage through tissue and cellular barriers. Current four-component lipid nanoparticles enable efficient endosomal escape and are a pivotal technology for the delivery of mRNA vaccines. However, challenges such as stability, availability, durability, and adverse effects persist. We have developed a self-assembling one-component ionizable amphiphilic Janus dendrimers (IAJD) delivery system with naturally occurring amino heads, capable of efficiently delivering mRNA to the spleen and lymph nodes. This single-component system simplifies synthesis, reduces development complexity, and enables rapid global distribution of mRNA vaccines during pandemics. As a proof of concept, one-component IAJD97, formulated with mRNA encoding norovirus mRNA capsid protein, demonstrates the potential of IAJDs as efficient delivery platform for mRNA vaccines, advancing their effectiveness and expanding applications to improve public health outcomes.