At 0.05 mg/kg luciferase mRNA (1 µg) and 6 h after intramuscular dosing, the aroLNP series showed lymph-node transfection with less liver signal than the SM-102 comparator. C6mPhE-383 was selected for follow-up biodistribution experiments.
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C6mPhE-383
Formulation & Performance
Published C6mPhE-383 LNP composition
| Component | mol% | Role |
|---|---|---|
| C6mPhE-383 | 35 | Ionizable lipid |
| DOPE | 16 | Helper phospholipid |
| Cholesterol | 46.5 | Sterol |
| C14-PEG2000 | 2.5 | PEG lipid |
| Total | 100 | Supporting Information §1.10 |
Results in the published mouse study
DiR-labeled C6mPhE-383 LNPs accumulated in draining iliac and inguinal lymph nodes with lower hepatic accumulation than SM-102 LNPs after intramuscular injection.
In a mouse SARS-CoV-2 spike mRNA prime–boost study (0.25 mg/kg, 5 µg mRNA; doses 3 weeks apart), C6mPhE-383 LNPs produced anti-RBD IgG and antigen-responsive T-cell responses. Spleens and serum were assessed 2 weeks after boosting.
In a separate luciferase mRNA experiment, circulating IL-6, TNF and IFN-γ were lower for C6mPhE-383 LNPs than for the SM-102 LNP comparator under the reported conditions.
Primary publicationYamagata HM, et al. Liver-Detargeted Aromatic Bioreducible mRNA Lipid Nanoparticles Confer Lymph Node Tropism and Robust Antigen-Specific Immunity. J Am Chem Soc (2026). doi:10.1021/jacs.6c00080. View paper. Formulation and synthesis: Supporting Information pp. 3 and 44; delivery and distribution: Figs. 2 and 4; vaccination and cytokines: Figs. 5 and 6.