Lipid S4
Datasheet

Product identity and specifications

Product description

Product overview Description & Application 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. RNA Delivery Brain delivery Extrahepatic delivery Classic ionizable lipids Cationic and ionizable lipids Featured lipid products

Handling guidance

Handling guidance Shipping, storage and sampling How is the lipid shipped, and how should I store it? We generally ship the neat (undissolved) lipid compound rather than an ethanol solution. The neat lipid is stable during transport with ice packs, and shipments originate from Shanghai. Pure form: store at −20 °C for up to 1 year. In solvent: store at −80 °C for up to 6 months or at −20 °C for up to 1 month. Keep sealed and protected from light. Avoid repeated thaw cycles for best results. Pure lipid or solution — which should I choose? Pure lipid is generally more stable during shipping and storage, so we usually recommend the pure form. A solution in ethanol or chloroform can be supplied when required by your workflow. Tell us the intended application, solvent and target concentration so the most suitable format can be confirmed. How should I measure a small amount of oily or viscous lipid? Ionizable lipids are often oily liquids or viscous semisolids, so material can be lost during repeated weighing or transfer. For a small pack, dissolve the entire quantity and aliquot it volumetrically. For example, add 1 mL ethanol to 25 mg lipid to prepare a 25 mg/mL stock, then use a pipette to withdraw the required amount. For quantities above 100 mg, direct weighing with an analytical balance may be more practical. Always confirm solvent compatibility and solubility first. Can you support formulation optimization and scale-up? Yes. Share the RNA cargo, target tissue, administration route, formulation method and assay plan. Our team can discuss starting molar ratios, N/P ratio and scale-up requirements for research workflows.

Formulation and performance

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Ordering

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References

• DOI: 10.1126/sciadv.adw0730