Lipid S4
Instructions for Use
Product information
Lipid S4 is an advanced ionizable lipid engineered for systemic mRNA delivery to the brain, leveraging SR-57227—a high-affinity 5-HT3 receptor ligand—as its core head group to enable targeted blood-brain barrier (BBB) penetration via receptor-mediated transcytosis, while incorporating amino linkers for pH-responsive ionization and biodegradable branched ester tails to facilitate efficient endosomal escape and intracellular mRNA release; optimized through orthogonal screening into OS4 LNP (formulated at S4/DOPE/Chol/DMG-PEG2k = 40:40:60:0.75 molar ratio), it demonstrated a 13.3-fold increase in brain mRNA expression compared to FDA-approved MC3 LNPs, and further conjugation with the Tat cell-penetrating peptide yielded OS4T LNP, boosting delivery efficiency by 12.7-fold over OS4 alone and enabling broad mRNA expression across neurons, astrocytes, microglia, and endothelial cells; validated in orthotopic glioblastoma models, OS4T delivered engineered IL-12 mRNA, suppressing tumor growth and extending median survival to 37 days (vs. 17 days for controls) with minimal systemic toxicity, positioning S4-based LNPs as a robust, translatable platform for CNS-targeted therapeutics.
| CAS No. | Not available |
| Chemical Name | Lipid S4 |
| Formula | C50H88N4O5 |
| M.Wt | 861.65 |
| Purity | ELSD-HPLC>95% |
| Storage | Original product: up to 1 year under the storage conditions stated on the vial, kept tightly sealed. Stock solutions: aliquots at -20°C, generally up to one month. |
| Shipping condition | Ships from Shanghai. Pure lipid is stable during ice-pack transport. |
Formulation & study context
Literature information refers to the cited study and its particular formulation. Administration routes are research context, not clinical instructions or a guarantee of performance.
A complete product-specific formulation has not been verified. No standard ratio is substituted.
| N/P ratio | Not reported in the verified record |
| Cargo | Not available in the verified record |
| Administration route | Not available in the verified record |
| Animal model | Not available in the verified record |
| Formulation process | Not available in the verified record |
N/P is the molar ratio of specified lipid nitrogen groups to nucleic-acid phosphate groups. A lipid:cargo mass ratio is a different quantity and must not be used as N/P.
Stock-solution preparation table
Calculated from the product-page molecular weight: 861.65 g/mol. Volumes are final solution volumes.
| Lipid mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 11.606 mL | 2.321 mL | 1.161 mL |
| 25 mg | 29.014 mL | 5.803 mL | 2.901 mL |
| 50 mg | 58.028 mL | 11.606 mL | 5.803 mL |
| 100 mg | 116.056 mL | 23.211 mL | 11.606 mL |
| 250 mg | 290.141 mL | 58.028 mL | 29.014 mL |
Volume (mL) = mass (mg) × 1000 / [MW (g/mol) × concentration (mM)]. These are mathematical conversions, not measured solubility or validated solvent recommendations. Confirm solvent compatibility and the molecular weight of the exact material before use.
Open editable solution calculators →Handling & storage
Provided that storage conditions are as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 1 year.
Wherever possible, prepare and use solutions on the same day. If stock solutions must be prepared in advance, store them as aliquots in tightly sealed vials at -20°C. Generally, these will be usable for up to one month.
Before use, and prior to opening the vial, allow the product to equilibrate to room temperature for at least 1 hour.
References
Lipid nanoparticles for mRNA delivery in brain via systemic administration- SCIENCE ADVANCES VOL. 11, NO. 33,2025