mRNAs For Tissue Regeneration 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.

Current regenerative approaches implement exogenous systems, comprising stem cells, scaffolds, growth factors, and plasmid DNA/viral vectors, that induce variable clinical results. An innovative approach that is safe, effective, and inexpensive is required. The lipid nanoparticle-encapsulated nucleoside-modified messenger RNA (mRNA) platform has proven to be a successful vaccine modality against coronavirus disease 2019, illustrating safety and high efficacy in humans. The same fundamental technology platform could be applied to stimulate the growth of mRNA-based regenerative therapy.

AstraZeneca and Moderna are developing AZD8601, a locally mRNA therapy that encodes for vascular endothelial growth factor A. In preclinical and phase 1 studies, it indicated the potential for regenerative angiogenesis. It is now being assessed for its ability to develop new cardiomyocytes and enhance parameters in patients with circumstances such as CVD and HF.

◆ mRNA therapeutics could depict the next-generation drug for tissue restoration in regenerative medicine.

◆ Non-immunogenic mRNA can be produced with the aim of modified nucleosides.

◆ Modification of the mRNA structure enables the synthesis of stable, non-immunogenic in vitro transcribed mRNA.

◆ Efficient delivery strategies, mainly designed for mRNA are indispensable for advancing mRNA therapeutics.

◆ mRNA loading and release from biomaterials is crucial for mRNA application to tissue restoration and must be progressed further.

PRODUCTION PROCESS 

Step 1. Plasmid Manufacturing 

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

Step 2. Transcrption 

In-vitro transcription (IVT)

In vitro transcription is a method that facilitates for 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 production

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.Y. Zhuang,  W. Cui, Biomaterial-based delivery of nucleic acids for tissue regeneration, Adv Drug Deliv Rev, 176 (2021), Article 113885.

2.U. Sahin, K. Kariko,  O. Tureci, mRNA-based therapeutics—developing a new class of drugs, Nat Rev Drug Discov, 13 (2014), pp. 759-780.

3.D. Weissman,mRNA transcript therapy, Expert Rev Vaccines, 14 (2015), pp. 265-281