Overview: mRNA vaccine - its key players, manufacturing and development process

mRNA vaccines have been at the forefront of medical innovation, especially during the COVID-19 pandemic. Here are general ideas of mRNA manufacturing and development process, and its key players:

MANUFACTURING OF A mRNA VACCINE

The manufacturing process for mRNA vaccines is fascinating and represents a significant leap in medical technology. Here is a summary of its manufacturing process:

In Vitro Synthesis: Unlike traditional protein expression, where cloning and amplification steps are time-consuming, mRNA is produced through an enzymatic in vitro synthesis process. This means there’s no need to remove cells or host cell proteins. The simplicity of this process allows for rapid adaptation to new protein targets, making it highly versatile.

mRNA Sequence Insertion: The heart of mRNA vaccine production lies in inserting a snippet of RNA code into a small DNA molecule within a cell. This process can be used for any mRNA sequence, making it remarkably flexible.

Reactor Tank Growth: Once the RNA code is inserted, the cell quickly grows more mRNA in a reactor tank. This streamlined approach contrasts with the customized, iterative setups required for conventional vaccines.

Purification and Formulation: Downstream processing involves purifying the mRNA product. One of the key advantages of mRNA vaccines is their sequence-independent manufacturing, which simplifies both upstream and downstream steps. This includes lipid nanoparticle (LNP) formulation and fill/finish processes.

DEVELOPMENT OF A mRNA VACCINE

The development of mRNA vaccines involves several crucial steps:

Design: At the onset of the COVID-19 pandemic, researchers rapidly sequenced the SARS-CoV-2 virus using state-of-the-art genomic sequencers. Scientists identified the spike protein gene as the vaccine candidate. The spike protein is important for the virus to attach to host cells.

Using in-vitro protocols, scientists create mRNA that mimics our natural biological processes. They separate the two strands of plasmid DNA and use RNA polymerase to transcribe the spike protein gene into a single mRNA molecule. This process closely resembles how our genes are transcribed. mRNA is a molecule that carries instructions from DNA to the cell's protein-making machinery.

Production: The designed mRNA is then produced in large quantities in the laboratory. This is done using a process called in vitro transcription (IVT). IVT uses enzymes to copy the mRNA sequence from a DNA template. The resulting mRNA is then purified to remove any unwanted contaminants.

Formulation: The purified mRNA is then formulated into a vaccine. This involves packaging the mRNA in a protective delivery system, such as lipid nanoparticles (LNPs). LNPs are tiny spheres made of fat molecules that help to protect the mRNA from degradation and deliver it to cells. 

most mRNA vaccines currently require ultra-cold storage to prevent degradation.

Preclinical testing: Once the vaccine has been formulated, it is tested in animals to assess its safety and efficacy. This is called preclinical testing.

Clinical trials: Clinical trials are studies that are conducted in humans to test the safety and efficacy of a vaccine.

Regulatory approval: If a vaccine is safe and effective in clinical trials, it can be submitted to regulatory agencies for approval.

SOME KEY PLAYERS

BioNTech: A German biotechnology company that collaborated with Pfizer to develop one of the first authorized mRNA COVID-19 vaccines1.

Moderna Therapeutics: An American biotech company that developed another highly effective mRNA COVID-19 vaccine.

Pfizer: Partnered with BioNTech to produce the BNT162b2 COVID-19 vaccine, which is an mRNA-based vaccine.

GreenLight Biosciences: GreenLight Biosciences is a US company, headquartered in Lexington, Massachusetts. They are a public-benefit corporation. Products include Calaritha, Varroa destructor mite-control product and a pipeline of other RNA-based solutions.

Strand Therapeutics: Strand Therapeutics is a US company. Based in Boston, Massachusetts, they focus on developing programmable mRNA therapeutics for various diseases, with a current emphasis on cancer.

These companies have played pivotal roles in advancing mRNA technology for both vaccines and therapeutics. Additionally, there are ongoing clinical trials exploring mRNA-based treatments for various diseases, including cancer and cardiovascular conditions. The potential of mRNA technology continues to expand, and researchers and industry players are actively enhancing their tools and technologies to harness its power.

HOW DOES A mRNA VACCINE WORK?

This article describes the general aspects of mRNA vaccine manufacturing and development. For accuracy and details for particular products, please check with the related scientific articles and patent applications, and related resources. 

REFERENCE

Ivana Knezevic, Development of mRNA Vaccines: Scientific and Regulatory Issues, Vaccines (Basel). 2021 Feb; 9(2): 81 

Yongjun Liang, et al, Development and Delivery Systems of mRNA Vaccines, Front Bioeng Biotechnol. 2021; 9: 718753.