LUMI-6|Ionizable Lipid for LNP

Cas No.:
Chemical Name:	LUMI6
Synonyms:	LUMI-6， LUMI 6
SMILES:	CCCCCCCCC(CCCCCC)C(=O)OCCCCCC(C(=O)NC12CC3CC(CC(C3)C1)C2)N(CCN1CCNCC1)C(=O)CCCCCBr
Formula:	C₄₅H₈₁O₄BrN₄
M.Wt:	822.07
Purity:	ELSD-HPLC>95%
Sotrage:	1 year -20°C
Publication:	https://www.biorxiv.org/content/10.1101/2025.02.14.638383v1.full.pdf

Cat. No.	Product name	Field of application
DC60793	LUMI6	The LUMI-6 lipid, autonomously designed via the LUMI-lab platform, is a brominated ionizable lipid optimized for mRNA delivery. Formulated at a molar ratio of 35:28:34.5:2 (LUMI-6:DOTAP:cholesterol:C14-PEG2000), LNPs exhibit uniform physicochemical properties, including a hydrodynamic diameter of ~80 nm, polydispersity index (PDI) <0.2, and robust mRNA encapsulation efficiency. In vitro, LUMI-6 LNPs demonstrated 1.8-fold higher transfection potency in human bronchial epithelial cells compared to its debrominated counterpart (LUMI-6D), with minimal cytotoxicity confirmed by CCK-8 assays. In vivo, pulmonary delivery of CRISPR-Cas9 mRNA via LUMI-6 LNPs achieved 20.3% gene editing efficiency in murine lung epithelial cells, surpassing SM-102 (Moderna’s clinical benchmark) and demonstrating preferential tropism for lung epithelium over endothelial cells—critical for inhaled therapies targeting cystic fibrosis and surfactant disorders. The brominated tail enhances endosomal escape through optimized protonation dynamics, though explicit pKa values remain unmeasured. Synthesized via high-throughput combinatorial chemistry and refined through AI-driven active learning, LUMI-6 combines scalable production with organ-selective delivery, positioning it as a transformative platform for pulmonary nucleic acid therapeutics.
DC60663	Si5-N14	Si5-N14 is a lipid-based molecule engineered with siloxane groups, designed specifically for efficient mRNA delivery to the lungs. The incorporation of siloxane units boosts the cellular uptake of mRNA-loaded lipid nanoparticles (LNPs) and enhances their ability to escape from endosomes. These properties significantly increase the overall effectiveness of mRNA delivery, making Si5-N14 a promising tool for targeted therapeutic applications.
DC65682	RCB-4-8	RCB-4-8 is a biodegradable ionizable lipid nanoparticle (LNP) engineered for efficient pulmonary mRNA delivery and in vivo genome editing, as detailed in the primary research article "Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing" (Li et al., Nature Biotechnology 2023）. Synthesized from a combinatorial library of 720 biodegradable lipids via a three-component reaction system, RCB-4-8 features an alkyne-containing lipid tail and tertiary amine headgroup, optimized through high-throughput screening for superior lung-targeting capabilities. Its unique molecular design incorporates hydrolyzable ester and carbonate groups, enabling rapid biodegradation (<30% lung retention at 48 h vs. >90% for conventional lipids) while maintaining high transfection efficiency. When formulated with DOTAP instead of DOPE, RCB-4-8 LNPs achieved 100-fold higher luciferase mRNA expression in murine lungs compared to FDA-approved MC3 LNPs and mediated 95% GFP knockout in vitro. In Ai9 reporter mice, intratracheal delivery of RCB-4-8 loaded with Cre mRNA edited 53% of total lung cells after three doses, while codelivery with Cas9 mRNA/sgRNA yielded 7.2% tdTomato⁺ cells, rising to 17% when combined with AAV-sgRNAs. With an optimal particle size of 85.7 nm (PDI 0.11) and >87% mRNA encapsulation, RCB-4-8 supports repeat dosing and represents a transformative platform for inhalable gene therapies targeting congenital lung diseases like cystic fibrosis.
DC60489	LIPID 331	Lipid 331 is a biodegradable cyclic ionizable lipid. LNPs containing Lipid 331 result in robust transfection in the nasal and lung tissues of mice and efficient transfection of lung epithelial cells and lung-resident APCs. Lipid 331 is a promising candidate for mRNA vaccine delivery, offering the potential for further enhancing the potency of mRNA vaccines.

LUMI6