Organ-selective LNPs: SORT lipids redirect delivery, but the mechanism is still debated
- The review covers selective organ targeting (SORT) lipid nanoparticles, where a fifth, charged lipid shifts payloads from the liver to lung or spleen in a dose-titratable way.
- The leading explanation, a changed protein corona that sidesteps the ApoE–LDL receptor route, has no consensus; lipid charge and pKa, hemodynamics and vascular fenestration may also contribute.
- Evidence is sorted into rodent, higher-order preclinical and clinical-adjacent tiers; most direct evidence still comes from rodents rather than primates or humans.
💡 Points Based on the abstract
Corona–tropism associations are stronger than causal evidence, which is exactly why I wouldn't project rodent organ selectivity onto a human dose. For anyone planning extrahepatic oligonucleotide or mRNA delivery, the next step is a head-to-head in non-human primates that measures biodistribution and cell-type uptake, not just reporter expression.