Membrane-destabilizing ionizable phospholipids: Novel components for organ-selective mRNA delivery and CRISPR–Cas gene editing

In a new study published in Nature Materials , Liu et al. 1 report a novel design of lipid nanoparticles (LNPs) in which multi-tailed ionizable phospholipids (iPhos) constitute the active component, and which facilitates endosomal escape and thus improves delivery of mRNA and/or single-guide (sg)RNA for in vivo gene editing. LNPs composed of the best-performing iPhos and different helper lipids—zwitterionic lipids, ionizable cationic lipids and permanently cationic lipids—achieved selective organ targeting (SORT) and organ-specific CRISPR-Cas9 gene editing in spleen, liver, and lungs of mice, respectively. 1