| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
None (excipient). 306-O12B LNPs target the liver; the ionizable lipid is neutral at physiological pH and becomes positively charged in acidic endosomes, facilitating RNA release into the cytosol.
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|---|---|
| ln Vitro |
306-O12B LNPs efficiently encapsulate and deliver RNA cargo in vitro. In HEK293 or HepG2 cells, LNPs loaded with luciferase mRNA demonstrate high transfection efficiency. For CRISPR-Cas9 applications, LNPs containing Cas9 mRNA and sgRNA lead to efficient gene editing at target loci (e.g., PCSK9 or TTR). The LNP delivery system using 306-O12B has been reported to be more efficient than MC-3.
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| ln Vivo |
In vivo, intravenous administration of 306-O12B LNPs encapsulating mRNA results in robust protein expression in the liver (e.g., ∼80-90% of hepatocytes transfected). For CRISPR-Cas9, LNPs deliver Cas9 mRNA and sgRNA, achieving >50% gene editing efficiency in the mouse liver after a single dose. 306-O12B LNPs are also effective for siRNA delivery, achieving potent and durable gene silencing in vivo.
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| Enzyme Assay |
306-O12B (typically supplied as a clear, viscous liquid) is dissolved in ethanol at a concentration of 10-50 mg/mL. It is mixed with helper lipids (e.g., DSPC, cholesterol, PEG2000-DMG) at optimized molar ratios (e.g., 50:10:38.5:1.5) and diluted with an acidic aqueous buffer (e.g., 25-50 mM sodium acetate, pH 4-5) containing nucleic acid (mRNA, siRNA) via microfluidic mixing. LNPs (size ∼80 nm) form spontaneously. Characterization includes DLS (size, PDI), zeta potential, encapsulation efficiency (>90%), and pKa measurement (~6.5-6.8).
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| Cell Assay |
In vitro transfection: cells (e.g., HEK293, HepG2, Huh-7) are seeded in 96-well plates (1×10⁴ cells/well) and treated with 306-O12B LNPs at mRNA doses of 0.01-1 ug/well for 6 h. Medium is replaced, and cells are incubated for 24-48 h. Efficacy is measured by luciferase activity or GFP fluorescence (reporter mRNA), or by quantifying target gene knockdown via qPCR (siRNA). Gene editing efficiency (CRISPR-Cas9) is measured by T7E1 assay or next-generation sequencing. Cytotoxicity is assessed by MTT assays.
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| Animal Protocol |
For in vivo studies, 306-O12B LNPs are administered intravenously via the tail vein to C57BL/6 or BALB/c mice (6-8 weeks old) at RNA doses of 0.2-1 mg/kg. For liver-specific delivery: reporter gene expression (luciferase) is assessed 6-24 h post-dose by bioluminescence imaging. For gene editing: tissues (liver) are harvested 1-4 weeks post-dose, genomic DNA is extracted, and editing efficiency at target loci (e.g., PCSK9, TTR) is assessed by NGS. Protein knockdown is confirmed by Western blot or ELISA. Biodistribution is assessed by measuring RNA levels in liver, spleen, and other organs via qRT-PCR.
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| ADME/Pharmacokinetics |
306-O12B LNPs demonstrate PK properties typical of LNP delivery systems. Following i.v. administration, LNPs have a circulation half-life of 2-6 h, with predominant accumulation in the liver (∼50-70% of injected dose) and spleen (∼10-20%). The ionizable lipid is cleared via metabolic degradation, with hydrolysis of ester linkages, followed by excretion of lipid components in bile and urine. Cmax in plasma typically occurs within 5-30 minutes post-injection.
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| Toxicity/Toxicokinetics |
306-O12B LNPs are generally well-tolerated at therapeutic RNA doses (0.2-2 mg/kg) in rodents. Mild, transient elevations in liver enzymes (ALT, AST) and pro-inflammatory cytokines (IL-6, IFN-gamma) may be observed within 6-24 h post-dose but return to baseline within 48-72 h. No significant histopathological changes in the liver or other organs have been reported at therapeutic doses. However, 306-O12B contains a sulfur-rich (thioketal) tail, which may impact its safety profile; longer-term studies are needed.
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| References | |
| Additional Infomation |
306-O12B (CAS 2566523-06-4, C₅₉H11₅N3O₈S₈, MW 1251.08) has >95% purity and is supplied as a liquid. Storage at -20degC is recommended. 306-O12B is a research-grade ionizable lipid for preclinical LNP formulation. No clinical trials have been reported. It is part of a family of 306-series lipids (including 306Oi10) optimized for RNA delivery to the liver. The lipid contains thioketal linkages (S-S bonds) that are biodegradable, potentially reducing toxicity.
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| Molecular Formula |
C59H115N3O8S8
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|---|---|
| Molecular Weight |
1251.08
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| Exact Mass |
1249.644
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| CAS # |
2566523-06-4
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| PubChem CID |
155374947
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| Appearance |
Colorless to light yellow liquid
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| LogP |
16.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
19
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| Rotatable Bond Count |
68
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| Heavy Atom Count |
78
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCCCCCCSSCCOC(=O)CCN(CCCN(C)CCCN(CCC(=O)OCCSSCCCCCCCC)CCC(=O)OCCSSCCCCCCCC)CCC(=O)OCCSSCCCCCCCC
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| InChi Key |
FTXIINBPTFOCHN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C59H115N3O8S8/c1-6-10-14-18-22-26-48-71-75-52-44-67-56(63)32-40-61(41-33-57(64)68-45-53-76-72-49-27-23-19-15-11-7-2)38-30-36-60(5)37-31-39-62(42-34-58(65)69-46-54-77-73-50-28-24-20-16-12-8-3)43-35-59(66)70-47-55-78-74-51-29-25-21-17-13-9-4/h6-55H2,1-5H3
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| Chemical Name |
2-(octyldisulfanyl)ethyl 3-[3-[3-[bis[3-[2-(octyldisulfanyl)ethoxy]-3-oxopropyl]amino]propyl-methylamino]propyl-[3-[2-(octyldisulfanyl)ethoxy]-3-oxopropyl]amino]propanoate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (79.93 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.00 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.00 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7993 mL | 3.9965 mL | 7.9931 mL | |
| 5 mM | 0.1599 mL | 0.7993 mL | 1.5986 mL | |
| 10 mM | 0.0799 mL | 0.3997 mL | 0.7993 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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