RCB-4-8
Datasheet

Product identity and specifications

Product description

Product overview Description & Application 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）. Identified from a library of 720 biodegradable lipids, 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. RNA Delivery Lung delivery Extrahepatic delivery Gene-editing delivery Classic ionizable lipids Ionizable lipid screening library Cationic and ionizable lipids Featured lipid products Pick-and-choose lipid library

Handling guidance

Handling guidance Shipping, storage and sampling How is the lipid shipped, and how should I store it? We generally ship the neat (undissolved) lipid compound rather than an ethanol solution. The neat lipid is stable during transport with ice packs, and shipments originate from Shanghai. Pure form: store at −20 °C for up to 1 year. In solvent: store at −80 °C for up to 6 months or at −20 °C for up to 1 month. Keep sealed and protected from light. Avoid repeated thaw cycles for best results. Pure lipid or solution — which should I choose? Pure lipid is generally more stable during shipping and storage, so we usually recommend the pure form. A solution in ethanol or chloroform can be supplied when required by your workflow. Tell us the intended application, solvent and target concentration so the most suitable format can be confirmed. How should I measure a small amount of oily or viscous lipid? Ionizable lipids are often oily liquids or viscous semisolids, so material can be lost during repeated weighing or transfer. For a small pack, dissolve the entire quantity and aliquot it volumetrically. For example, add 1 mL ethanol to 25 mg lipid to prepare a 25 mg/mL stock, then use a pipette to withdraw the required amount. For quantities above 100 mg, direct weighing with an analytical balance may be more practical. Always confirm solvent compatibility and solubility first. Can you support formulation optimization and scale-up? Yes. Share the RNA cargo, target tissue, administration route, formulation method and assay plan. Our team can discuss starting molar ratios, N/P ratio and scale-up requirements for research workflows.

Formulation and performance

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Ordering

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References

• DOI: 10.1038/s41587-023-01679-x