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

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.