cKK-E12

cKK-E12 is a high-potency ionizable amino lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of nucleic acids, particularly messenger RNA (mRNA). Originally identified through a combinatorial library of tail-branched amino lipids, cKK-E12 is designed to optimize the delivery efficiency and safety profile of mRNA therapeutics. Its mechanism involves pH-dependent protonation; at physiological pH, it remains relatively neutral, but in the acidic environment of the endosome, it becomes positively charged, facilitating endosomal membrane disruption and the subsequent release of mRNA into the cytoplasm. In preclinical studies, cKK-E12 has been successfully employed to deliver CRISPR-based epigenetic editors (such as CRISPRoff) to silence the MGMT gene in glioblastoma, as well as to deliver cytokine-encoding mRNAs like IL-2 for cancer immunotherapy. It has demonstrated superior delivery performance in various tissues, including the liver and intracranial tumors.

Other names

1,1'-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl)(2-hydroxydodecyl)amino)ethyl)piperazin-1-yl)ethyl)azanediyl)bis(dodecan-2-ol)