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Lipid 5D8

Version 1.79da4318 · 2026-09-13

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CAS No.Not available
Chemical NameLipid 5D8
SynonymsLipid-5D8
SMILESCCCCCCCCOC(=O)CC(NCCCN(CCCN(C)C)C(CC(=O)OCCCCCCCC)C(=O)OCCCCCCCC)C(=O)OCCCCCCCC
FormulaC48H93O8N3
M.Wt840.28
Purity>98%
StorageOriginal product: up to 1 year under the storage conditions stated on the vial, kept tightly sealed. Stock solutions: aliquots at -20°C, generally up to one month.
Shipping conditionShips from Shanghai. Pure lipid is stable during ice-pack transport.
Publicationhttps://www.biorxiv.org/content/10.1101/2025.02.25.640222v1

Lipid 5D8 is a novel biodegradable ionizable lipid (IL) developed through a combinatorial chemistry strategy to overcome the limitations of conventional lipid nanoparticles (LNPs) in mRNA delivery. Synthesized via a one-step, solvent-free Michael addition reaction between amine and thiol monomers, 5D8 features asymmetric lipid tails and a biodegradable ester backbone, ensuring both structural versatility and reduced toxicity. In preclinical studies, 5D8-based LNPs demonstrated exceptional liver-targeting efficiency and mRNA delivery performance. A single intravenous dose (1 mg/kg) achieved 61% CRISPR-Cas9-mediated editing of the TTR gene in mice, reducing serum TTR protein by 90%, outperforming benchmark lipids like C12-200 (51% editing). Moreover, 5D8 enabled efficient delivery of base editors (ABE8.8 and CBE4max), achieving 42% PCSK9 editing (74% serum protein reduction) and correcting hereditary tyrosinemia in mice, significantly extending survival. Beyond gene editing, 5D8 LNPs effectively delivered siRNA (complete serum TTR clearance at 0.05 mg/kg) and enhanced hepatocyte targeting by enriching apolipoprotein E on particle surfaces. Crucially, 5D8 exhibited superior biocompatibility with no hepatotoxicity (normal ALT/AST levels), contrasting traditional LNPs. Its rapid biodegradability and "plug-and-play" design make 5D8 a versatile platform for mRNA therapeutics, holding broad potential for treating genetic disorders, cardiovascular diseases, and beyond. This innovation represents a critical advancement toward safer, high-efficiency clinical translation of gene-editing therapies.L

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