Blog How to make a messenger RNA vaccine: inside the RNA manufacturing process November 9, 2020 Messenger RNA Manufacturing Overview Messenger RNA vaccines are a new category. Curious about how messenger RNA manufacturing and how it is made into a vaccine? Check out our primer below. If you’d like to find out more about how to create vaccines at scale, then have a look at our article on breaking the vaccine production bottleneck. RNA Manufacturing: How to make a messenger RNA based vaccine The process of making a messenger RNA vaccine can be essentially divided into three parts: building the molecule; purifying the solution; and formulating it for delivery. Step One: Building the molecule GreenLight takes a length of DNA that codes for the protein they want – the template. They put that into a vat full of free nucleotides, and enzymes will – just as in nature – start grabbing those nucleotides out of solution, making RNA copies of the DNA template. The GreenLight system uses very simple nucleotides, which are made as byproducts of many biochemical processes and are often used in the production of baby formula. GreenLight encourages them to react by adding a catalyst, an enzyme, just as in your cells. This reduces the amount of energy required to start the reaction. Step Two: Purifying the solution The process of building the molecule rapidly produces lots of the high quality RNA sections that you want, but they are still swimming in a soup of free nucleotides and enzymes. You have to purify away all the things you used to make the messenger RNA by, in essence, filtering your material in a tube, which separates out the RNA molecules you want. GreenLight is developing a water- based model, which involves no toxic waste, and which – while not yet cheap – is at least less expensive, with systems that can be scaled up to industrial levels. Step Three: Formulating it for delivery RNA molecules are delivered via lipid nanoparticles. Some lipid (fat) molecules have an interesting property: one end of each molecule is attracted to water molecules (hydrophilic), and the other end is repelled by them (hydrophobic). When mixed with water and other molecules, such as RNA, the hydrophobic ends will huddle around the RNA, forming little spheres with the hydrophilic ends on the outside. These tiny particles, less than a thousandth of a millimeter across, can make it through the outer membranes of our bodies’ cells, and deliver the RNA into the mechanisms within (the ribosomes), where they can start making proteins.