246C10
Instructions for Use
Product information
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. To obtain iLNPs that could specifically target liver sinusoidal endothelial cells (LSECs), six different ionizable lipids (241C10 to 246C10) were synthesized by an epoxide ring-opening reaction with piperazine- or piperidine-containing amines. 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.
| CAS No. | Not available |
| Chemical Name | 246C10 |
| Formula | C58H120N4O4 |
| M.Wt | 937.60 |
| 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: 937.6 g/mol. Volumes are final solution volumes.
| Lipid mass | 1 mM | 5 mM | 10 mM |
|---|---|---|---|
| 10 mg | 10.666 mL | 2.133 mL | 1.067 mL |
| 25 mg | 26.664 mL | 5.333 mL | 2.666 mL |
| 50 mg | 53.328 mL | 10.666 mL | 5.333 mL |
| 100 mg | 106.655 mL | 21.331 mL | 10.666 mL |
| 250 mg | 266.638 mL | 53.328 mL | 26.664 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
[1]. Kim M, et al. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver. Sci Adv. 2021;7(9):eabf4398. Published 2021 Feb 26.