Table 2.
Targeting properties and other major characteristics of representative SORT-LNPs
| Target organ | Cell types | Key lipid/SORT molecular | Formulation: the active lipid/helper lipid/cholesterol/DMG-PEG/SORT molecular (mol %) | Efficiency |
|---|---|---|---|---|
| Liver | Sinusoidal endothelial cell (SEC) | 5A2-SC8/DODAP | 5A2-SC8/DOPE/cholesterol/C14-PEG2K/DODAP = 19/19/38/4/20 | Liver-targeted SORT LNPs (20% DODAP) delivered Cre mRNA to ∼93% of all hepatocytes42 |
| Lung | Epithelial cells, endothelial cells, immune cells | 5A2-SC8/DOTAP | 5A2-SC8/DOPE/cholesterol/C14-PEG2K/DOTAP = 16.7:16.7:33.3:3.3: 30 | Lung-targeted SORT LNPs (50% DOTAP) transfected ∼40% of all epithelial cells, ∼65% of all endothelial cells and ∼20% of immune cells in the lungs42 |
| Lung | Basal cell | DOTAP40/DOTAP | 5A2-SC8/DOPE/cholesterol/PEG-DMG/DOTAP = 36/20/40/4/40 | Transfected ∼60% of NGFR+ basal cell populations after treatment123 |
| Lung | Endothelial cells; epithelial cells, immune cells | 5A2-SC8/18:1 TAP, 18:1 RI, or 18:0 EPC | 5A2-SC8/DOPE/cholesterol/C14-PEG2K/SORT molecules = 11.9/11.9/23.8/2.4/50 | 83% of the total luminescent flux produced in the lungs; endothelial cells were most efficiently transfected, followed by epithelial cells, then immune cells48 |
| Spleen | B cells, T cells, macrophages | 5A2-SC8/18PA | 5A2-SC8/DOPE/cholesterol/C14-PEG2K/18PA = 16.7:16.7:33.3:3.3: 30 | Spleen-targeted SORT LNPs (30% 18PA) transfected ∼12% of all B cells, ∼10% of all T cells, and ∼20% of all macrophages42 |
| Spleen | T cells | 5A2-SC8/18 : 1 PA LNPs | 5A2-SC8/DOPE/cholesterol/PEG-DMG/18:1PA = 15/15/30/3/7 | 5.8% of CD8+ T cells and 5.5% of CD4+ T cells were transfected124 |
| Spleen | / | 4A3-SC8/BMP | 4A3SC8/DOPE/cholesterol/DMG-PEG/BMP = 15: 15: 30: 3: 20 | LNP contained anionic BMP exhibited preference for spleen delivery over liver delivery125 |
| Lymph node | Antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs) | 113-O12B | 113-O12B/cholesterol/helper lipid/DMG-PEG = 16: 4.8: 3: 2.4 | Positive mRNA expression in ∼27% DCs and ∼34% macrophages126 |
DODAP, ionizable cationic lipid 1,2-dioleoyl-3-dimethylammonium-propane; DOTAP (18:1 TAP), the permanently cationic SORT molecule 1,2-dioleoyl-3-trimethylammonium-propane; 18PA, negatively charged 1,2-dioleoyl-sn-glycero-3-phosphate; 18:1 RI, the trimethylammonium propane (TAP) lipid series, which nearly shares the same chemical structure as 18:1 TAP but substitutes one of the methyl groups in the head group with an ethanol motif; 18:0 EPC, the ethylphosphocholine (EPC) series lipid; BMP: bis(monoacylglycerol)phosphate.