mRNAs For Cancer Immunotherapy 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. With our comprehensive experience and advanced platform, we can give a series of mRNA-based replacement therapy services. We are excited to partner with our clients on the journey of bringing novel mRNA-based therapies to the clinical application.

Immunotherapy is treatment that employs specific parts of a person’s immune system to fight diseases such as cancer. This can be accomplished in a pair of ways:

◆ Stimulating, or boosting, the natural protection of your immune system so it helps harder or smarter to find and attack cancer cells

◆ Formulating substances in a lab that are just like immune system components and utilizing them to enable restore or enhance how your immune system helps to find and attack cancer cells

mRNA vaccines have become a favourable forum for cancer immunotherapy. During vaccination, naked or vehicle-loaded mRNA vaccines efficiently express tumour antigens in antigen-presenting cells (APCs) and promote APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine settings due to high efficacy, safe administration, rapid development potentials, and cost-effective manufacturing. Nonetheless, mRNA vaccine applications have been restricted by instability, innate immunogenicity, and ineffective in vivo delivery.

Reasonable mRNA structure changes (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to withstand these issues. Adapting the administration routes and co-delivery of numerous mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further improved the host anti-tumour immunity and boosted the likelihood of tumour cell eradication. 

With the current U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the profitable therapeutic effects of mRNA cancer vaccines achieved in various clinical trials against multiple aggressive solid tumours, Further the rapid advancement of mRNA vaccines for cancer immunotherapy in the near future. 

PRODUCTION PROCESS 

Step 1. Plasmid Manufacturing 

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

Step 2. Transcription 

In-vitro transcription (IVT)

In vitro transcription is a method that facilitates the template-directed synthesis of RNA molecules of any sequence from short oligonucleotides to those of various kilobases in μg to mg quantities. It is based on the engineering of a template that contains a bacteriophage promoter sequence (e.g. from the T7 coliphage) upstream of the sequence of interest fulfilled by transcription utilizing the corresponding RNA polymerase.

Step 3. mRNA purification

After certain manufacturing steps it is significant to purify the mRNA. 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.

Step 4. mRNA encapsulation and polishing

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

Step 5. QC release and stability testing

Relying on your final mRNA application and clinical stage, the quality control testing requirements may vary.

◆ 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 specific application or program needs

◆ Vast variety of modification, treatment, and purification options

◆ Accessible 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 physiological environment.

References

1.Irving M (29 March 2022). "Implantable immunotherapy "factory" fights cancer faster, more effectively". New Atlas. Retrieved 29 March 2022.

2.Weiner LM, Surana R, Wang S (May 2010). "Monoclonal antibodies: versatile platforms for cancer immunotherapy". Nature Reviews. Immunology. 10 (5): 317–27.

3.Malone RW, Felgner PL, Verma IM. Cationic liposome-mediated RNA transfection. Proc Natl Acad Sci. 1989;86(16):6077–81.