The ionizable cationic lipid DLin-MC3-DMA is an effective vector for siRNA delivery. DLin-MC3-DMA (MC3) was discovered by Thomas Madden and Michael Hope during their exploration of novel ionizable lipids. It was used as a key component in Onpattro, the first siRNA drug approved by the FDA in 2018 (Onpattro also marks the first-ever targeted RNA-based gene therapy administered via a non-viral vector).
| Product Name | DLin-MC3-DMA |
| Chemical Name | 4-(dimethylamino)-butanoic acid, (10Z, 13Z)-1-(9Z, 12Z) -9, 12-octadecadien-1-yl-10, 13-nonadecadien-1-yl ester |
| CAS No. | 1224606-06-7 |
| NMPA CDE registration no. | / |
| USFDA DMF No. | / |
| Quality grade | Injection |
| Quality standards | Manufacturer's standard |
| Molecular Formula | C43H79NO2 |
| Applications and examples | DLin-MC3-DMA is a fully synthetic ionizable cationic lipid that is suitable for liposomal formulations of DNA,RNA, and various nucleic acid drugs. Compared to conventional cationic lipids, it significantly improves nucleic acid drug encapsulation efficiency and transfection efficiency, making it an excellent membrane material for cationic liposomes. It has been widely used in the research and clinical applications of RNA drug liposomes and is utilized in the marketed siRNA liposome product, Onpattro. |
| Product code | O02006 |
| Package sizes | 1g, 5g |
| Storage condition | The product should be stored and transported under an inert gas atmosphere, in a sealed and light-protected container at a temperature of −20 ± 5°C. It should be kept away from strong oxidizing agents. Retest every 12 months when stored properly. |
1. Low toxicity: DLin-MC3-DMA is a pH-responsive ionizable lipid, whereby it adopts a positive charge at low pH and has near-neutral charge at physiological pH. This means that, when forming lipid nanoparticles (LNPs) encapsulating nucleic acids under acidic conditions, it exhibits minimal positive charge density in the bloodstream, resulting in low cellular toxicity.
2. High efficiency: LNPs formed with DLin-MC3-DMA exhibit positive charge, facilitating lysosomal SiRNA escape to enhance transfection efficiency and reducing phagocytosis by macrophages.
DLin-MC3-DMA is a colorless to yellowish oily liquid with a pKa of 6.44. The functional activity of LNPs is correlated with the pKa value of the cationic lipid used. LNPs formed with DLin-MC3-DMA with a pKa of 6.2 to 6.5 exhibit higher gene-silencing activity.
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