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mRNA Manufacturing & Formulation

mRNA technology and lipid nanoparticle (LNP) delivery systems have revolutionized vaccine development. Delivery of an mRNA payload into the cytosol of a cell can induce target protein production. The target protein then serves as an antigen to trigger an immune response, offering protection against subsequent exposure. Unprecedented results for mRNA vaccines against SARS-CoV-2 have implications that go far beyond the COVID-19 pandemic and offer a compelling therapeutic strategy in the fight against a broad range of genetic diseases and infectious agents, as well as for protein replacement therapy.

Development and manufacturing of mRNA and LNP drug products for therapeutic applications and vaccines are simple, scalable, and rapid. Given the ability to compress timelines, while maintaining a robust safety and efficacy profile, mRNA technology is well suited for response to outbreaks, pandemics, and diseases with unmet needs.

mRNA Manufacturing Workflow

Unleashing the power of mRNA technology to revolutionize how diseases are treated and prevented relies on robust and consistent processes to make the mRNA and then purify and formulate it. Success requires use of high-quality products with superior performance and services provided by experts with extensive experience and a proven track record of success in this emerging field.

Our mRNA manufacturing template provides a robust workflow, while our LNP manufacturing processes ensure a high-quality and consistent supply.

Contract Development and Manufacturing Services

Our integrated capabilities include the development and manufacture of functional mRNAs, synthetic long RNAs and DNAs as well as an offering of mRNA technology products, such as RNA isolation and mRNA amplification kits. We are committed to direct and flexible customer interactions with life science industries and academic research institutions around the world, including on-site technical support. With our proven workflow, mRNA manufacturing is highly reproducible, and the final product has superior activity. Key features of our offering include:

  • Production of fully customizable sequences up to 13,000 nucleotides
  • A significantly lower requirement (~10,000x) for plasmid DNA compared to standard mRNA manufacturing processes
  • Highly reproducible process yielding mRNA with a homogeneous poly A tail and high performing product

Products and Services for mRNA Manufactures

  • Production of a plasmid DNA (pDNA) template
  • Linearization of pDNA with unique restriction site enzyme
  • Removal of the restriction enzyme, BSA, DNA fragments, endotoxins, and other impurities using tangential flow filtration (TFF) and chromatography
  • Transcription of linearization of pDNA in mRNA using bacteriophage RNA polymerase
  • Addition of 5’ cap structure to mRNA to ensure stability and efficient transduction in the cell

mRNA Purification

Following in vitro transcription, mRNA is purified from the impurities and materials used in the previous steps including endotoxins, immunogenic double-stranded RNA (dsRNA), residual DNA template, RNA polymerase, and elemental impurities. Several options are available for mRNA purification.

Products and Services for mRNA Purification

  • Tangential flow filtration (TFF) provides efficient separation from small impurities not retained by the membrane. Molecular weight cut-offs ranging from 30 to 300 kDa can be used based on the mRNA size. With TFF it is possible to purify, concentrate, and diafilter the product within the same unit operation.
  • Several chromatography techniques can be used, including reverse-phase ion pair, anion exchange, and affinity chromatography using poly(dT) capture. Chromatography is used following enzymatic capping to remove unwanted products and oligonucleotide impurities
  • A final concentration and diafiltration step is performed to maximize product purity and transfer the mRNA into the appropriate buffers for formulation or storage. At this stage, mRNA can be further purified, concentrated, and diafiltered within the same unit operation.

mRNA Formulation

Naked mRNA is unstable and drug delivery systems, such as lipid nanoparticles (LNP), are necessary to deliver mRNA to target cells. The quality of raw materials used to synthesize lipids, as well as the lipid type and source have a direct impact on the impurity profile, particle characteristics, particle stability, and final formulation release profile. We offer a variety of custom and portfolio lipids to design the most appropriate LNP for your mRNA application.

mRNA Protection

Production of stable mRNA requires a robust process and use of chemicals and raw materials that minimize degradation risk by RNAse activity or microbial contamination. To protect mRNA during manufacturing, purification, and formulation, our high-quality Emprove® Expert raw materials are tested for endonuclease activity and have low bioburden and endotoxin levels. Our raw materials also comply with IPEC-PQG GMP requirements.

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