In recent years, great progress has been made into mRNA vaccine development, especially in individualized tumor vaccines. mRNA vaccines are a promising approach as the production process is simple, safety profiles are better than those of DNA vaccines, and mRNA-encoded antigens are readily expressed in cells. Efficient entry of mRNA vaccines into human cells is a very challenging process. As an exogenous nucleic acid, naked mRNA is easily recognized by the immune system and rapidly degraded by nucleases like RNases or microbial contamination after entering the body. Therefore, the pharmacological effects of using naked mRNA as a vaccine are greatly reduced. That challenge is the key to successful mRNA manufacturing, purification, and formulation. To improve the immune efficiency of mRNA vaccines, special delivery systems are required to protect administered mRNA from nucleases and allow delivery into cells.
Equipped with a team of professional scientists, Seattle Genova is capable of providing specialized support in the design, production, and evaluation of mRNA formulation services. Our mRNA manufacturing template provides a robust workflow, while our lipid nanoparticle (LNP) manufacturing processes ensure a high-quality and consistent supply.
mRNA Delivery Technologies
Seattle Genova provides a wide set of mRNA formulation technologies, which are listed below:
1.Viral vector construction for mRNA delivery
Seattle Genova provides the mRNA formulation services using viral vectors (AdVs), adeno-associated viruses (AAVs), and lentivirus vectors (LVs). The virion structure protects the mRNA from degradation by host enzymes while in the body or tissue. Once viruses enter target cells, they replicate within the host cells to permit long-term expression.
2.Non-viral vector construction for mRNA delivery
Seattle Genova also offers the non-viral vector formulations of mRNA, which are subdivided into lipid or lipid materials and polymer delivery systems. The hybrid system of lipid and polymer are also advantage for mRNA delivery.
3.Polymer synthesis for Polymer-based Delivery of mRNA
Seattle Genova provides the mRNA formulation services using spermine, polyethyleneimine, chitosan, and polyurethane. At present, common polymer delivery systems are poly-amido-amine (PAA), poly-beta amino-esters (PBAEs) and polyethylenimine (PEI).
4.Lipid based particle production for mRNA delivery
Lipid nanoparticles (LNPs) are currently the most advanced delivery system for mRNA vaccines. Originally used for the delivery of siRNA, LNPs have been proven to be safe and effective. LNPs are stable particles composed of a lipid bilayer shell of cationic lipids, auxiliary lipids, cholesterol and polyethylene glycol (PEG) encompassing an aqueous core, in which they can carry a mRNA payload.
5.Peptide conjugated mRNA production
Conjugation with cell-penetrating peptides (CPPs) has been shown to improve protein transduction into the cells. Here at Seattle Genova, we formulate your mRNA using CPPs, which are short peptides, typically less than 30 amino acids long, and can be fused or conjugated with mRNA to penetrate cellular membranes.
6.Virus-Like Replicon Particle production for mRNA delivery
The virus-like particle (VLP) system is a form of non-viral delivery technology, as does not contain viral genomic nucleic acid and does not replicate in the host cell. VLP is produced through the self-assembly of viral structural proteins. The appearance of VLP is similar to a native virus, but they lack the viral genome, so they are entirely replication-incompetent.
7.Cationic Nanoemulsion production for mRNA delivery
Cationic liposomes were the first liposome delivery materials used in mRNA vaccines. Positively charged cationic lipids can aggregate with negatively charged mRNA through electrostatic interactions to form a multi-layer cystic complex called a lipoplex (LP). This system has been used for the delivery of mRNA vaccines against the respiratory syncytial virus (RSV), HIV and human cytomegalovirus (CMV).
8.Naked mRNA Vaccine Production
Seattle Genova also offers a formulation of mRNA vaccine that can be delivered without any additional carriers, that is, in a naked format. In this method, mRNA is dissolved in buffer and then injected directly. Local injection of naked mRNA can lead to expression of different proteins in mouse muscle tissue.
9.Dendritic Cells-Based mRNA Vaccine production
Dendritic cells (DCs) are types of antigen presenting cells (APCs) that present processed antigens from microorganisms, tumor cells and virus-infected cells to T-cells for the generation of the immune response. Seattle Genova also provides it as mRNA delivery in vaccine. DCs are suitable vaccination targets because of their migration to T-cells in the lymph nodes, high expression of MHC, co-stimulators and cytokines.
10.Co-delivery of mRNA Vaccines
Incorporating an adjuvant that is non-lipid is key to the activation of the cytotoxic T-cells. This is because the presence of an adjuvant is important for dendritic cell maturation, which is another necessity for cytotoxic T-cell activation. For example, co-delivery of mRNA and gardiquimod (adjuvant) led to the effective antigen expression and DC maturation in vitro.
11.mRNA electroporation service
Electroporation disrupts the cell membrane by generating electric shock for intracellular nucleic acid delivery. Delivery efficiency can be improved by adjusting voltage, capacitance, resistance and other factors, such as cell number, density, RNA quantity and pulse time.
12.RNApatch production for mRNA delivery
Seattle Genova also provides mRNA-loaded dissolving microneedles (RNApatch) technology. This technique is fabricated using the micromolding method followed by physical and functional characterization. The RNApatch is mechanically strong and is capable of mediating cutaneous delivery of naked mRNA. Transfection efficiency and kinetics improved with increased RNApatch needle lengths and are comparable with subcutaneous injection.
13.Lyophilization of lipid nanoparticle-formulated mRNA
The long-term storage of mRNA-LNP vaccines without freezing is still a challenge to maintain their high expression, and no decrease in the immunogenicity in the research. Lyophilization (freeze-drying) is commonly used in the pharmaceutical industry to increase the stability and shelf life of various products by removing the water from drug formulations.
14.Polymer-lipid hybrid particle production for mRNA delivery
Recently, lipid polymer hybrid nanoparticles (LPNs), by integrating the complementary properties of lipid and polymeric nanomaterials, are emerging as a class of nanomaterials for RNA delivery. Previous study was identified a lead LPNs formulation, PLGA4-7 LPNs (one of PLGA polymers), which demonstrated significantly enhanced mRNAs delivery efficiency in vitro.
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