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Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles
Author(s) -
Li Yamin,
Jarvis Rachel,
Zhu Kuixin,
Glass Zachary,
Ogurlu Roza,
Gao Peiyang,
Li Peixuan,
Chen Jinjin,
Yu Yingjie,
Yang Yongjie,
Xu Qiaobing
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202004994
Subject(s) - in vivo , in vitro , chemistry , messenger rna , transfection , biochemistry , biophysics , biology , microbiology and biotechnology , gene
Abstract Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).