Sterols

Scientists and researchers are continually exploring innovative strategies to improve the efficacy and safety of RNA delivery systems. One such strategy capitalizes on the unique properties and versatility of sterols, offering exciting opportunities to enhance the delivery of RNA therapy.

Understanding Sterols

Sterols are a class of lipids that play a critical role in cell membranes, providing structural integrity and regulating membrane fluidity. Cholesterol is the best-known sterol and is found in large quantities in mammalian cells.

Sterols such as cholesterol are not typically used as major components of RNA delivery vehicles. Instead, they are usually incorporated into lipid formulations to modulate the stability, rigidity or fluidity of the lipid bilayer. This affects the overall properties of the nanoparticles and their performance in RNA delivery.

Figure 1. Biomimetic nanocarrier eLNP incorporating β-sitosterol. Left: The chemical structure of beta-sitosterol differs from cholesterol by one ethyl group. Right: Schematic diagram of endosomal escape of eLNP^[1].

Function of Sterols

• Enhance RNA stability

RNA molecules are susceptible to degradation by enzymes present in body fluids, limiting their therapeutic potential. Sterols, such as cholesterol, have been shown to increase the stability of RNA molecules.

By incorporating cholesterol into a lipid-based delivery system, researchers improved the protection of the RNA cargo, allowing efficient delivery to target cells and tissues.

• Promote cellular uptake

Efficient uptake of RNA molecules by target cells is critical for successful therapeutic outcomes. Sterols can promote cellular uptake by modulating the physicochemical properties of lipid delivery systems. The presence of sterols such as cholesterol in lipid formulations can promote the formation of stable, well-defined nanoparticles that facilitate the entry of RNA cargo into cells.

• Regulates endosomal escape

After cellular uptake, RNA molecules often encounter endosomes, which prevents their release into the cytoplasm to exert therapeutic effects. Sterols have shown promise in promoting endosomal escape. By incorporating sterols with specific properties into the delivery system, researchers can promote disruption of endosomal membranes, allowing efficient release of RNA molecules into the cytoplasm.

What we offer

Alfa Chemistry supplies a wide range of sterol products to companies working on vaccines. We also tailor sterols to our customer's specific requirements for efficient RNA delivery.

Researchers at Alfa Chemistry are actively exploring various sterol modifications to optimize their potential for RNA delivery. These modifications include the conjugation of sterols to target ligands for specific cell recognition, the incorporation of pH-responsive moieties for triggered release, and the use of sterol-based nanoparticles for increased stability and controlled release.

Reference

1. Golubovic, A; et al. Bioinspired Lipid Nanocarriers for RNA Delivery. ACS Bio Med Chem Au. 2023, 3(2): 114-136.

Our products and services are for research use only and cannot be used for any clinical purposes.

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