RCB-4-8 |Ionizable Lipid for LNP

Cas No.:	2941228-91-5
Chemical Name:	bis((Z)-12-(((non-2-yn-1-yloxy)carbonyl)oxy)octadec-9-en-1-yl) 3,3’-((2-(diethylamino)ethyl)azanediyl)dipropionate
Synonyms:	RCB-4-8
SMILES:	CCN(CC)CCN(CCC(OCCCCCCCC/C=C\CC(CCCCCC)OC(OCC#CCCCCCC)=O)=O)CCC(OCCCCCCCC/C=C\CC(CCCCCC)OC(OCC#CCCCCCC)=O)=O
Formula:	C₆₈H₁₂₀N₂O₁₀
M.Wt:	1125.7
Purity:	>95%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Publication:	Li, B., Manan, R.S., Liang, S.-Q., et al. Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing. Nat. Biotechnol.

Description:

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.

References:

Li, B., Manan, R.S., Liang, S.-Q., et al. Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing. Nat. Biotechnol.

MSDS

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.
DC49907	5A2-SC8	5A2-SC8 is a dendrimer for miRNA delivery to late-stage liver tumors with low hepatotoxicity. 5A2-SC8 shows potent EC50 < 0.02 mg/kg (siRNA against FVII (siFVII)) in dose-response experiments, and well tolerated in separate toxicity studies in chronically ill mice bearing MYC-driven tumors. 5A2-SC8 is a degradable lipid-like compound (ester-based dendrimer) for small RNAs delivery.5A2-SC8, was obtained by screening a large library of more than 1500 ester-based dendrimers containing ionizable amino groups, which have three tertiary amine heads and five lipid tails. Based on this library, the in vitro transfection efficiency of different formulations of 5A2-SC8 iLNPs was evaluated, discovering the optimal formulation (5A2-SC8, DOPE, cholesterol, PEG at a molar ratio of 15:15:30:3) of 5A2-SC8 iLNPs for delivering fumarylacetoacetate hydrolase (FAH) mRNA to liver.After the intravenous injection via tail, the model mice of hepatorenal tyrosinemia type I had strong FAH protein expression, which prevented body weight loss and increased the survival rate of hepatorenal tyrosinemia mice . In addition to introducing utility of 5A2-SC8 iLNPs for the therapeutic intervention, the 5A2-SC8 iLNPs containing DOTAP have been used to establish complex mouse models via intravenous injection, including in situ liverspecific cancer model and in situ lung-specific cancer model. Based on this iLNPs delivery system, 5A2-SC8 induced model construction method overcomes the time-consuming and costly disadvantages of traditional animal models establishing methods, including transgenesis and gene engineering in embryonic stem cells.