mRNA-based Vaccines Services

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 gives a robust workflow, while our lipid nanoparticle (LNP) manufacturing processes ensure a high-quality and consistent supply. 

mRNA has risen to the surface as a favourable solution for dealing with future pandemics as well as other infectious diseases such as rabies, Zika, and cytomegalovirus infection. Various mRNA-based products are also in clinical pipelines for cystic fibrosis and several cancers. The COVID-19 pandemic accelerated research and improvement of this technology as a vaccine platform, directing mRNA vaccines becoming the early modality to obtain emergency use authorization and then approval for SARS-CoV-2 in the U.S.

Vaccination with non-viral vectors provided nucleic acid-based vaccines mimics infection or immunization with live microorganisms. mRNA technology promises to dramatically alter the traditional approach to vaccine development. The underlying standard is delivery of a transcript that encodes one or more immunogens into the host cell cytoplasm, where translation produces immunogenic proteins that are later sequestered intracellularly, integrated into the cell membrane, or secreted.

Clinical Applications of mRNA vaccines

Cancer

The majority of early work with mRNA vaccines has concentrated on cancer. Simply, conventional vaccine strategies are not applicable to such non-infectious diseases. Cancer vaccines are therapeutic, rather than prophylactic, constructed to target tumor-associated antigens expressed preferentially by cancerous cells and, as an outcome, to facilitate cell-mediated immune responses capable of reducing the tumor burden.

 Analysis of mRNA to induce adaptive immune responses to cancer started in 1995, when Conry and coworkers reported that protective antitumor immunity could be induced in mice by intramuscular injection of mRNA encoding carcinoembryonic antigens. Presently, more than 100 clinical trials for mRNA vaccines are documented by the U.S. National Library of Medicine for a broad range of cancers that comprises breast, ovarian, prostate, colon, metastatic renal cell, glioblastoma, melanoma, and solid tumors.

Infectious Diseases

Conventional vaccines are largely prophylactic, built to prevent infectious diseases.Traditional approaches to formulate new vaccines are challenged by requirements for rapid development and large scale implementation. In this regard, an amount of recent reports indicated the potency and versatility of mRNA vaccine establishes to elicit protection against a broad variety of infectious agents (e.g., Zika virus, rabies, influenza virus, Ebola virus, Streptococcus species, and Toxoplasma gondii) in animal samples. mRNA-based vaccines constructs indicated the ability to produce potent neutralizing antibody responses in animals immunized with only one or two low doses.

Allergies and Autoimmune Diseases

While current research efforts are directed on cancer and infectious diseases, the outcomes of recent animal studies indicate the potential use of RNA vaccines to prevent or treat allergies and autoimmune diseases. Allergen-specific immunotherapy is a beneficial treatment for type I hypersensitivity reactions. 

PRODUCTION PROCESS 

DNA plasmid production for mRNA synthesis

mRNA synthesis starts with plasmid design and production. Plasmids are generated in bacterial cultures, then harvested and purified.

In-vitro transcription (IVT)

In vitro transcription is a procedure that authorizes for template-directed synthesis of RNA molecules of any sequence from short oligonucleotides to those of several kilobases in μg to mg quantities. It is founded on the engineering of a template that includes a bacteriophage promoter sequence (e.g. from the T7 coliphage) upstream of the sequence of interest pursued by transcription utilizing the corresponding RNA polymerase.

mRNA purification

mRNA purification eliminates enzymes, remaining nucleotides, plasmid DNA, and defective mRNA. New emerging technologies like Fibro chromatography, currently accessible for mAb purification, are in development for molecules such as DNA plasmids and mRNA.

mRNA encapsulation and polishing

The purified mRNA-based therapeutic is formulated in lipid nanoparticles (LNPs) as a drug delivery vehicle. Core chromatography can be utilized to further eliminate impurities.

QC release and stability testing

◆ RNA content by UV-Vis

◆ Purity by IRRP HPLC

◆ Residual DNA by RT-qPCR

◆ Residual protein by MS

◆ Potency by cell-free translation

◆ Endotoxin and residuals measurements

◆ Sequencing

SERVICE HIGHLIGHTS

◆ High quality products and services at competitive prices

◆ Custom-tailored assistance to meet particular application or program needs

◆ Broad variety of modification, treatment, and purification options

◆ Reasonable custom synthesis up to gram scales of mRNA and long RNA (multiple kilobases)

◆ In-house plasmid manufacturing optimized for therapeutic mRNA generation

DELIVERABLES

We provide high throughput evaluations along with faster results. In addition to that, we provide many different mRNA formulation services to meet your various end-point in vaccine delivery. These formulations come with specific functionality to improve the efficiency of vaccines in the physiologicall environment.

REFERENCES

1.Rauch, S.; Jasny, E.; Schmidt, K.E.; Petsch, B. New Vaccine Technologies to Combat Outbreak Situations. Front. Immunol. 2018, 9,1963. 

2.Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273. 

3.Pronker, E.S.; Weenen, T.C.; Commandeur, H.; Claassen, E.H.; Osterhaus, A.D. Risk in vaccine research and development quantified. PLoS ONE 2013, 8, e57755.

4.Plotkin, S.; Robinson, J.M.; Cunningham, G.; Iqbal, R.; Larsen, S. The complexity and cost of vaccine manufacturing—An over-view. Vaccine 2017, 35, 4064–4071. 

5.Pollard, A.J.; Bijker, E.M. A guide to vaccinology: From basic principles to new developments. Nat. Rev. Immunol. 2020, 21, 1–18.

6.Pardi, N.; Hogan, M.J.; Weissman, D. Recent advances in mRNA vaccine technology. Curr. Opin. Immunol. 2020, 65, 14–20.