4A3-SC8

4A3-SC8 is an ionizable cationic lipid (pK_a = 6.66) and a dendrimer that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA, mRNA, single-guide RNA (sgRNA), ssDNA, and PEGylated BODIPY dyes.^1,2,3,4 LNPs containing 4A3-SC8 and encapsulating siRNA targeting Factor VII selectively accumulate in the liver and decrease hepatic Factor VII activity in mice.¹ Intratumoral administration of LNPs containing 4A3-SC8 and encapsulating homologous double-strand repair (HDR) elements correct the DNA encoding GFP with a tyrosine-to-histidine mutation at position 66 (GFP^Y66H) in a HEK293 mouse xenograft model.³ Intravenous administration of LNPs containing 4A3-SC8 and encapsulating an mRNA reporter and a PEGylated BODIPY dye have been used for tumor imaging in mice.⁴

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1. Zhou, K., Nguyen, L.H., Miller, J.B., et al. Modular degradable dendrimers enable small RNAs to extend survival in an aggressive liver cancer model. Proc. Natl. Acad. Sci. USA 113(3), 520-525 (2016).

2. Álvarez-Benedicto, E., Farbiak, L., Ramírez, M.M., et al. Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA). Biomater. Sci. 10(2), 549-559 (2022).

3. Farbiak, L., Cheng, Q., Wei, T., et al. All-in-one dendrimer-based lipid nanoparticles enable precise HDR-mediated gene editing in vivo. Adv. Mater. 33(30), e2006619 (2021).

4. Xiong, H., Liu, S., Wei, T., et al. Theranostic dendrimer-based lipid nanoparticles containing PEGylated BODIPY dyes for tumor imaging and systemic mRNA delivery in vivo. J. Control. Release 325, 198-205 (2020).