mRNA-based Protein Replacement Drug Development

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.

Presently, mRNA-based therapeutics has shown its tremendous potential in the treatment of several human diseases, particularly for malignant tumors. mRNA delivery systems have been regarded as safe and transient techniques with a high transduction capacity in disease therapies. In recent researches, a new mRNA-based protein replacement therapy has been constructed based on replacing the uridine residues in mRNA with nucleoside pseudouridine. The outcomes have indicated that this therapy can interrupt innate immune responses resulted in by RNase and Toll-like receptors, reducing the expression level of several cytokines and preventing the immunogenicity during treatment.

mRNA-based replacement therapy to fighting illnesses, comprising multi-genic- and multi-factorial—like metabolic and cardiovascular diseases, as well as infectious disease prevention. 

As a professional expert in the field of mRNA therapeutics advancement, Seattle Genova offers a one-stop mRNA-based platform for our customers, to design and synthesize suitable mRNA constructs, to generate safe and effective mRNA-based replacement therapies, as well as to evaluate the properties of mRNA-based therapies.

WORKING PROCESS 

DNA plasmid production for mRNA synthesis

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

In-vitro transcription (IVT)

In vitro transcription is a technique that allows 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 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.

mRNA purification

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

mRNA encapsulation and polishing

The purified mRNA-based therapeutic is developed 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 help to meet specific application or program needs

◆ Large 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 production

DELIVERABLES

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

Reference

1.Crunkhorn, S.; et al. Regulatory watch: enhanced chance of success for protein replacement therapies. Nat Rev Drug Discov. 2013, 12(6): 414.

2.Van, H. L.; et al. How mRNA therapeutics are entering the monoclonal antibody field. Journal of Translational Medicine. 2019, 17(1).