Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing.

Li, Bowen; Manan, Rajith Singh; Liang, Shun-Qing; Gordon, Akiva; Jiang, Allen; Varley, Andrew; Gao, Guangping; Langer, Robert et al. · Nat Biotechnol · 2023

basic_science · Level V

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Abstract

The expanding applications of nonviral genomic medicines in the lung remain restricted by delivery challenges. Here, leveraging a high-throughput platform, we synthesize and screen a combinatorial library of biodegradable ionizable lipids to build inhalable delivery vehicles for messenger RNA and CRISPR-Cas9 gene editors. Lead lipid nanoparticles are amenable for repeated intratracheal dosing and could achieve efficient gene editing in lung epithelium, providing avenues for gene therapy of congenital lung diseases.

Medical subject headings