Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo

可生物降解电离脂质的即插即用组装,用于体内有效的 mRNA 递送和基因编辑

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作者:Xuexiang Han, Ying Xu, Adele Ricciardi, Junchao Xu, Rohan Palanki, Vivek Chowdhary, Lulu Xue, Ningqiang Gong, Mohamad-Gabriel Alameh, William H Peranteau, James M Wilson, Drew Weissman, Michael J Mitchell2

Abstract

mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for plug-and-play assembly of diverse biodegradable ionizable lipids and identify a lead candidate that produces superior lipid nanoparticles for various gene editing tools delivery in vivo. Our study highlights the utility of this synthetic approach and the generality of this platform for potent in vivo gene editing.

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