246C10
Datasheet

Product identity and specifications

Product description

Product overview Description & Application 246C10 is a synthesized ionizable lipid. 246C10 can be formulated into lipid nanoparticles (LNPs) with dioleoylphosphatidylethanolamine (DOPE), cholesterol, and C16-PEG2000 ceramide (PEG-lipid) as well as mRNA. The lipid nanoparticle formulations can be used for mRNA delivery. Six ionizable lipids (241C10 to 246C10) were evaluated for liver sinusoidal endothelial cell (LSEC) delivery. Biodistribution and gene regulation of various iLNPs were assessed in vivo, and the results showed that the 246C10 iLNPs (containing piperazine amine) had the highest luciferase expression in the liver. When further analyzing the 246C10 iLNPs transfection efficiency in different types of liver cells, it was found that tdTomato fluorescence was mainly concentrated in hepatocytes, not in LSECs. Figure 6f shows that 80% of hepatocytes are fluorescent, 40% of LSECs are fluorescent, and 20% of Kupffer cells are fluorescent. Due to the mannose receptor on LSECs, mannose-PEG lipid was introduced into 246C10 iLNPs to alter the distribution of iLNPs in different liver cells. As shown in Figure 6g, tdTomato fluorescence distribution was 15% of hepatocytes, 70% of LSECs, and 15% of Kupffer cells, significantly improved the ability of iLNPs to actively target LSECs. In contrast, this work indirectly shows that the iLNPs with piperazine head lipid are more able to deliver mRNA to the liver and translate the target protein than the iLNPs with piperidine head lipid. It is worth mentioning that the preparation buffer of 246C10 iLNPs could influence the encapsulation efficiency of mRNA. With the addition of sodium chloride in the citrate buffer, the encapsulation efficiency of CRISPR-Cas9 mRNA and sgRNA was increased. These iLNPs were able to treat hemophilia safely, without causing hepatotoxicity, the immune response induced by Cas9 and off-target editing. RNA Delivery Macrophage delivery Classic ionizable lipids Ionizable lipid screening library Cationic and ionizable lipids Featured lipid products Pick-and-choose lipid library Additional lipid-related products Liver delivery

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.abf4398
• Primary article