LUMI-6|brominated ionizable lipid |DC Chemicals

Cas No.:
Purity:	98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	https://www.biorxiv.org/content/10.1101/2025.02.14.638383v1.full.pdf

Description:

LUMI-6, a brominated ionizable lipid developed through xAI’s LUMI-lab platform, features a unique molecular design with a bromine atom critical for enhancing mRNA delivery, outperforming its debrominated derivative, LUMI-6D. In murine models, it achieved a groundbreaking 20.3% gene editing efficiency in lung epithelial cells via inhaled delivery of CRISPR-Cas9 lipid nanoparticles (LNPs), surpassing previous records and the commonly used SM-102 LNP in pulmonary Cas9 mRNA/gRNA complex delivery. In human bronchial epithelial (HBE) cells, LUMI-6 demonstrated 1.8-fold higher mRNA transfection efficiency than LUMI-6D while maintaining comparable cytotoxicity to non-brominated lipids. Its brominated tail structure optimizes mRNA encapsulation and release, balancing high efficiency with low toxicity. Notably, LUMI-6 exhibits cellular selectivity, preferentially transfecting lung epithelial cells—such as ciliated (α-tubulin+) and club (CCSP+) cells—over endothelial cells, making it highly relevant for airway-targeted therapies like cystic fibrosis and surfactant disorders. Effective for both mRNA delivery and CRISPR-Cas9 systems, LUMI-6 represents a significant advancement in pulmonary gene therapy, addressing unmet needs in treating congenital lung diseases through epithelial cell-specific editing. As the first reported LNP to achieve over 20% editing efficiency in lung epithelium via inhalation, it underscores the power of AI-driven lipid discovery in accelerating therapeutic innovation.

References:

https://www.biorxiv.org/content/10.1101/2025.02.14.638383v1.full.pdf

MSDS

Cat. No.	Product name	Field of application
DC12145	DLinDMA	DLinDMA is a key lipid component of stable nucleic acid lipid particles as a benchmark.
DC33580	DODMA	DODMA, also known as MBN 305A is a a cationic lipid containing the unsaturated long-chain (18:1) oleic acid inserted at both the sn-1 and sn-2 positions. It has been used in the composition of lipospomes formulated as stable nucleic acid lipid particles that can encapsulate siRNA or other small molecules to be used for drug delivery
DC33635	DODAP	DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.
DC59010	C14-4 (C14-494,Lipid B-4,Lipid B4)	C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.
DC33636	DOTAP	DOTAP, also known as 1,2-Dioleoyl-3-trimethylammoniumpropane, is a cationic liposome-forming compound used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. It has been used in gene delivery vectors for gene ther
DC31000	LP-01	LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.
DC52028	MVL5	MVL5 is a new Multivalent Cationic Lipid for siRNA Delivery.Improved total gene silencing and Lower non-specific gene silencing,Lower toxicity.
DC53130	93-O17S	93-O17S is an imidazole-based synthetic lipidoid for in vivo mRNA delivery. Lipid nanoparticles (LNPs) with 93-O17S promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist).
DC57046	ATX-126(ATX-0126, lipid 10p)	ATX-126(ATX-0126, 10p) is an ionizable cationic lipid (pKa = 6.38).It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA. Intravenous administration of LNPs containing ATX-126(ATX-0126, 10p) and encapsulating Factor VII siRNA decrease Factor VII blood levels in mice.
DC59002	ssPalmO-Phe(SS-OP)	ssPalmO-Phe(SS-OP) is a self-degradable material for the delivery of oligonucleotides. ssPalmO-Phe is a self-degradable derivative of ssPalm that is self-degraded in the intraparticle space by a specific hydrolytic reaction. ssPalmO-Phe is beneficial for overcoming the plasma/endosomal membrane, LNP-ssPalmO-Phe can be used to deliver both nucleic acids.