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.
246C10是一种可电离的阳离子脂质（pKa=6.75）[1]。246C10可以与二油基磷脂酰乙醇胺 （DOPE）、胆固醇、C16-PEG2000神经酰胺（PEG-lipid）等脂质结合，用于生成脂质纳米颗粒（LNP），用于将RNA治疗药物靶向递送到细胞中[2, 3]。246C10与编码荧光素酶（mFLuc）的mRNA以及DOPE、胆固醇、PEG-脂质和甘露糖-PEG脂质一起配制成LNP，通过静脉注射处理ApoE敲除小鼠，可显著增加肝脏中的荧光素酶表达[4]。使用负载Cas9和sgRNA的246C10 LNP对小鼠肝脏中的AT进行靶向基因编辑，可抑制小鼠抗凝血酶（AT）的生成，而不会引入脱靶效应、肝毒性和大量抗Cas9免疫反应[5]。