Description
C12-200 is a branched-chain ionizable cationic lipidoid with five hydroxyl groups. It has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA, siRNA, or self-amplifying RNA (saRNA). The hydroxyl groups enables further derivatization or replacement with other reactive functional groups.
Uses
C12-200 is a type of ionizable cationic lipid and helper lipid commonly used for mRNA delivery. In the hemophilia B mouse model, mRNA encoding human erythropoietin (EPO) and coagulation factor IX (FIX) can be successfully delivered and expressed using C12-200. C12-200 is utilized in research related to hemophilia B[1][2][3].
in vivo
C12-200 (0.25 or 0.5 mg/kg, i.v., single injection) delivers exogenous human mRNA, producing target proteins at supraphysiological levels. Human erythropoietin (EPO) and coagulation factor IX (FIX) demonstrate potent pharmacodynamic effects in the KO mouse model[2].
| Animal Model: | Hemophilia B (FIX knockout (KO)) mouse model[2] |
| Dosage: | 0.25 or 0.5 mg/kg |
| Administration: | Intravenous injection (i.v.), single injection |
| Result: | led to plasma FIX levels of 400 ng/ml and 1.77 μg/ml with doses of 0.25 and 0.50 mg/kg, respectively, in KO mice. And C12-200 resulted in a significant increase in activity in the treated mice. |
References
[1] Khare P, et al. Development of Lipidoid Nanoparticles for siRNA Delivery to Neural Cells. AAPS J. 2021;24(1):8. Published 2021 Dec 6. DOI:
10.1208/s12248-021-00653-2[2] DeRosa F, et al. Therapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system. Gene Ther. 2016;23(10):699-707. DOI:
10.1038/gt.2016.46[3] Kauffman KJ, et al. Optimization of Lipid Nanoparticle Formulations for mRNA Delivery in Vivo with Fractional Factorial and Definitive Screening Designs. Nano Lett. 2015 Nov 11;15(11):7300-6. DOI:
10.1021/acs.nanolett.5b02497
