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

Han, X.; Xu, Y.; Ricciardi, A.; Xu, J.; Palanki, R.; Chowdhary, V.; Xue, L.; Gong, N.; Alameh, M.-G.; Pereanteau, W.; Wilson, J. M.; Weissman, D.; MITCHELL, M.

2025-03-01 bioengineering
10.1101/2025.02.25.640222 bioRxiv
Show 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.

Published in Proceedings of the National Academy of Sciences (predicted rank #6) · training set

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