![]() ![]() Reagan, Houping Ni, Drew Weissman, Virgil Percec. Maurya, Matthew Liu, Qi Xiao, Juncheng Lu, George Lauri, Nathan Ona, Erin K. Journal of the American Chemical Society 2021, 143 Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes. Johnson, Sumanta Chatterjee, Di Zhang, Sang M. Shuai Liu, Xu Wang, Xueliang Yu, Qiang Cheng, Lindsay T.Dynamic Glycopeptide Dendrimers: Synthesis and Their Controllable Self-Assembly into Varied Glyco-Nanostructures for the Biomimicry of Glycans. Feihu Bi, Jin Zhang, Zengming Wei, Deshui Yu, Shuai Zheng, Jie Wang, Hongyu Li, Zan Hua, Hui Zhang, Guang Yang.The Journal of Physical Chemistry Letters 2022, 13 Opportunities and Challenges for mRNA Delivery Nanoplatforms. Yuyan Zhang, Yingying Hu, Huayu Tian, Xuesi Chen.Synthetic Conjugated Oligoelectrolytes Are Effective siRNA Transfection Carriers: Relevance to Pancreatic Cancer Gene Therapy. Chengbin Yang, Haoqiang Huang, Nishtha Manish Singh, Cheng Zhou, Guang Yang, Zhourui Xu, Haoming Lin, Gaixia Xu, Ken-Tye Yong, Guillermo C.Journal of the American Chemical Society 2022, 144 The Unexpected Importance of the Primary Structure of the Hydrophobic Part of One-Component Ionizable Amphiphilic Janus Dendrimers in Targeted mRNA Delivery Activity. Maurya, Qi Xiao, Matthew Liu, Jasper Adamson, Nathan Ona, Erin K. Atochina-Vasserman, Juncheng Lu, Devendra S. Amphiphilic Dendrimer Vectors for RNA Delivery: State-of-the-Art and Future Perspective. Jiaxuan Chen, Dandan Zhu, Xiaoxuan Liu, Ling Peng.Lipid-Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Components. Trojan Horse Delivery of Spherical Nucleic Acid Probes into the Cytoplasm for High-Fidelity Imaging of MicroRNAs. Kefeng Wu, Qiang Li, Chi Yao, Dayong Yang, Dingbin Liu.Helper-Polymer Based Five-Element Nanoparticles (FNPs) for Lung-Specific mRNA Delivery with Long-Term Stability after Lyophilization. Yan Cao, Zongxing He, Qimingxing Chen, Xiaoyan He, Lili Su, Wenxia Yu, Mingming Zhang, Huiying Yang, Xingxu Huang, Jianfeng Li.An All-in-One Bioorthogonal System for Precise Cancer Therapy. Si Wu, Lu Zhang, Yue Wei, Tingting Cui, Jinsong Ren, Xiaogang Qu.What’s Next after Lipid Nanoparticles? A Perspective on Enablers of Nucleic Acid Therapeutics. ![]() Ritam Das, Pintu Kanjilal, Jewel Medeiros, S.Journal of the American Chemical Society 2023, 145 Self-Assembly of Glycerol-Amphiphilic Janus Dendrimers Amplifies and Indicates Principles for the Selection of Stereochemistry by Biological Membranes. Dapeng Zhang, Qi Xiao, Mehrnoush Rahimzadeh, Matthew Liu, Cesar Rodriguez-Emmenegger, Yusuke Miyazaki, Wataru Shinoda, Virgil Percec.This article is cited by 14 publications. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs. Some, exhibiting organ specificity, are stable at 5 ☌ and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the “PEG dilemma”, and the stability at only very low temperatures limit their efficiency. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. ![]()
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