'Tripod-like' lung-targeting (LuT) lipids for highly efficient and selective LNPs for gene delivery and editing - PubMed
5 hours ago
- #lipid nanoparticles
- #gene delivery
- #CRISPR-Cas9
- Development of 444 lung-targeting lipids (LuT lipids) for efficient mRNA and CRISPR-Cas9 delivery to lungs.
- Top-performing LuT lipids feature a 'tripod-like' structure with a quaternary amine head and three long alkyl chains.
- LuT lipids enhance endosomal escape, cargo release, and endogenous targeting via plasma protein adsorption.
- Lead 1A7B13 LNPs show 25.5-fold improvement in mRNA delivery and 9.2-fold increase in gene-editing efficiency.
- 1A7B13 LNPs achieve over 90% lung selectivity and effectively deliver IL-10 mRNA in acute lung injury models.
- Study reveals structure-activity relationships, enriching the toolkit for lung-specific carriers.