246C10 is an ionizable cationic lipid (pKa = 6.75)[1]. 246C10 can be combined with lipids such as dioleylphosphatidylethanolamine (DOPE), cholesterol, and C16-PEG2000 ceramide (PEG-lipid) to generate lipid nanoparticles (LNPs) for targeted delivery of RNA therapeutics into cells[2, 3]. 246C10 was formulated into LNPs together with mRNA encoding luciferase (mFLuc) and DOPE, cholesterol, PEG-lipid, and mannose-PEG lipid. When injected intravenously into ApoE knockout mice, it significantly increased luciferase expression in the liver[4]. Targeted gene editing of AT in mouse livers using 246C10 LNPs loaded with Cas9 and sgRNA inhibited the production of mouse antithrombin (AT) without introducing off-target effects, liver toxicity, and a large anti-Cas9 immune response[5].
References:
[1] Tang X, Zhang Y, Han X. Ionizable Lipid Nanoparticles for mRNA Delivery[J]. Advanced NanoBiomed Research, 2023, 3(8): 2300006.
[2] Jin H, Jeong M, Lee G, et al. Engineered lipid nanoparticles for the treatment of pulmonary fibrosis by regulating epithelial‐mesenchymal transition in the lungs[J]. Advanced Functional Materials, 2023, 33(7): 2209432.
[3] Wu S, Lin L, Shi L, et al. An overview of lipid constituents in lipid nanoparticle mRNA delivery systems[J]. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2024, 16(4): e1978.
[4] Kim M, Jeong M, Hur S, et al. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver[J]. Science advances, 2021, 7(9): eabf4398.
[5] Liu Z, Li Z, Li B. Nonviral delivery of CRISPR/Cas systems in mRNA format[J]. Advanced NanoBiomed Research, 2022, 2(11): 2200082.