DLin-MC3-DMA

Описание

D-Lin-MC3-DMA (MC3, DLin-MC3-DMA) is a potent and ionizable cationic lipid. D-Lin-MC3-DMA is used for delivery of siRNA in vivo. DLin-MC3-DMA, or (6Z,9Z,28Z,31Z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino)butanoate , is one of the most utilized cationic lipids that is used for making Lipid Nano-Particles (LNPs). These lipids, can form nanoparticles that can encapsulate and deliver siRNA, mRNA, DNA or small molecules into the cytoplasm and represent the most advanced delivery platforms for systemic administration of active molecules.

Использование

DLin-M-C3-DMA is a commonly used drug delivery vehicle for the fabrication of lipid nanoparticles (LNPs), which exert therapeutic effects by encapsulating and delivering siRNA, mRNA, DNA, or small molecules into the cytoplasm of the cell, and is a potent siRNA delivery vehicle.

Определение

(6Z,9Z,28Z,31Z)-heptatriacont-6,9,28,31-tetraene-19-yl 4-(dimethylamino)butanoate (DLin-MC3-DMA or MC3, liquid oil) was identified as one of the most promising ionizable lipids due to its high transfection efficiency and is used in the first FDA-approved drug for the treatment of amyloidosis. In 2020, Ermilova et al. derived parameters for MC3 in combination with the Slipids force field. Unfortunately, the authors did not parametrize the protonated state of the MC3 molecule. Since MC3 has an apparent pKa of about 6.44, the protonated state plays an essential role: it ensures efficient encapsulation of the nucleic acids at low pH and a high charge at endosomal pH, enabling the drug release from the LNP. At physiological pH, the MC3 lipids are neutral, enabling the circulation of largely uncharged LNPs. For the modelling, it is beneficial to parametrize both states simultaneously[1].

Биологическая активность

DLin-MC3-DMA is an ionizable lipid used in combination with other lipids for encapsulation of RNA and DNA into lipid nanoparticles (LNPs). Administration of DLin-MC3-DMA based LNPs have delivered siRNA and reduced Factor VII levels in mice. Delivery of BCR-ABL siRNA reduced leukemic burden in a mouse model of chronic myeloid leukemia (CML).