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