6Ac1-C12|degradable ionizable lipid

Cas No.:
Chemical Name:	6Ac1-C12
Synonyms:	6Ac1C12，， 6Ac1 C12
SMILES:	CCCCCCCCCCCCNCCC(=O)OCC(COCC(COC(=O)CCN(C)CCCCCCCCCCCC)(COC(=O)CCN(C)CCCCCCCCCCCC)COC(=O)CCN(C)CCCCCCCCCCCC)(COC(=O)CCN(C)CCCCCCCCCCCC)OC(=O)CCN(C)CCCCCCCCCCCC
Formula:	C₁₀₄H₂₀₄O₁₃N₆
M.Wt:	1746.81
Purity:	ELSD-HPLC>95%
Sotrage:	1 year -20°C
Publication:	GAO X, et al. Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation[J]. Nature Communications, 2024, 15(1): 5740.

Description:

6Ac1-C12 is an ester-core degradable ionizable cationic lipid designed for mRNA delivery, featuring a unique hexa-acrylate ester core ("6Ac1") conjugated with six N-methyldodecylamine chains ("C12") via solvent-free Michael addition. This branched architecture enables optimal mRNA encapsulation and confers exceptional stability, maintaining consistent ~100 nm particle size for over 30 days at 4°C—crucial for cold-chain storage. With a pKa ≈ 6.0, it facilitates pH-responsive endosomal escape through membrane fusion (80% FRET signal increase at pH 5.5) and efficient cytoplasmic mRNA release.Its composition allows precise organ targeting: in conventional four-component LNPs, 98% hepatic mRNA expression occurs post-IV administration, primarily in endothelial cells (60% transfection efficiency). Cholesterol removal enables lung-specific accumulation and translation via three-component formulations, overcoming historical hepatic off-targeting. The lipid shows negligible cytotoxicity in vitro (>85% cell viability) and no significant organ damage in vivo (ALT/AST/BUN/CREA levels comparable to PBS controls). Its degradable ester core hydrolyzes into smaller metabolites, enhancing biocompatibility. Modular compatibility with DOTAP/DDAB cationic lipids expands applicability for pulmonary or splenic targeting, establishing 6Ac1-C12 as a versatile platform for organ-selective mRNA therapeutics.

References:

Su, K. et al. Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation. Nat. Commun.2024

Cat. No.	Product name	Field of application
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