Cationic nanoemulsion (CNE) is a very effective nonviral delivery system to successfully deliver therapeutic mRNA. Moreover, it can improve the transfection of nucleic acids and has been evaluated as one hybrid vector for delivering self-amplifying mRNA vaccines. As an undoubted leader in mRNA services, Creative Biolabs is uniquely positioned to address mRNA synthesis & modification & delivery with our unparalleled, multiplexed mRNA platform. We now offer different options for effective mRNA delivery, such as lipid-based vectors, polymer-based vectors and hybrid vectors to protect mRNA from degradation by extracellular RNases.
Manipulating gene expression with mRNA has shown significant advantages over viral DNA delivery, such as the lower risk of immune reactions and integration into the host genome, etc. In mRNA therapeutics, a safe and effective delivery system often determines the success rate that can protect mRNA against ubiquitous ribonucleases (RNases), facilitate their entry into cells and subsequent release into the cytoplasm, and target them to lymphoid organs or particular cells. Recent advances in nanotechnology and material science have yielded many promising nonviral mRNA delivery systems, amongst which, hybrid vector is one important type whose hybrid formulations normally integrate potential advantages of different components and provide more flexibility compared with non-hybrid systems.
CNEs are mainly composed of two parts: one is the cationic lipid DOTAP (1,2-dioleoyl-sn-glycero-3-phosphocholine) that can be added to the oil phase to bind the mRNA electrostatically; the other is the emulsion adjuvant MF59 that is an oil-in-water emulsion consisting of squalene and surfactants. This combination can effectively deliver self-amplifying mRNA and elicit immune responses as potent as those triggered by viral vectors in mice, rabbits, and non-human primates.
CNEs used as mRNA delivery vehicles show several obvious advantages: 1) they can be produced on an industrial scale with relatively low cost; 2) they are stable during storage and are highly biocompatible; 3) they have shown higher transfection and lower toxicity than liposomes.
CNEs are usually fabricated by the probe sonication method. Based on the components of CNEs (an oil, cationic surfactant, osmotic agent, phospholipids and 0.2 μm double-filtered distilled water), the production processes include the following steps:
Fig.2 Preparation of CNE and CNE-mRNA complexation. (Brito, 2014)
Services at Creative Biolabs
With deep and broad expertise in the targeted delivery of mRNA therapeutics, Creative Biolabs understands that the exogenous mRNA needs to be appropriately formulated to be protected from degradation by extracellular RNases. Our scientists have developed multiple mRNA delivery formulations, each designed for different functions and optimized for therapeutic product needs based on the intended application and route of delivery to meet specific demands. Our mRNA delivery formulation can ensure the appropriate delivery of the RNA to the intended site of action. In addition to formulation development and mRNA complexation services, we also provide one-stop mRNA services, expanding from mRNA synthesis, modification, delivery, stability test to other downstream applications services to accelerate the progress of your mRNA project.
Fig.3 Vectors for mRNA delivery. (Tan, 2018)
Efficient mRNA delivery is critical to achieving effective therapeutic relevance. CNEs formulation displays good condensation, efficient cytosolic delivery and lower cytotoxicity for mRNA delivery. Creative Biolabs is devoted to offering mRNA delivery vehicle optimization services as a stand-alone service or part of a complete mRNA therapeutics package for global customers. If you are interested in our services, please feel free to contact us.