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EMBL facilities support development of RNA vaccines

Biotechnology company BioNTech and Johannes Gutenberg University Mainz conduct collaborative research with EMBL scientists at the beamline P12 in Hamburg

The image shows the beamline P12 at EMBL Hamburg. In the centre, several cylindrical elements are connected into a pipe-like structure. In the front, it is connected to a white box-shaped device, and several smaller devices and cables visible around. There is also a grid visible around the beamline.
The beamline P12 at EMBL Hamburg allows studying the structure of molecules in solution using small-angle X-ray scattering (SAXS) technique. Svergun group/EMBL

BioNTech, the biotech company that together with Pfizer recently presented the first positive results for a COVID-19 vaccine, used one of EMBL Hamburg’s facilities at DESY‘s PETRA III X-ray source for their research on vaccine development. BioNTech, together with Johannes Gutenberg University Mainz, Tel Aviv University, Leiden University, and Forschungszentrum Jülich, recently published results of several studies on how RNA can be better packaged and delivered into human cells.

The vaccine candidates from BioNTech and Pfizer, as well as those from biotech company Moderna, belong to a new class of vaccines that use messenger RNA (mRNA): an instruction-carrying molecule that tells a cell to make a specific protein. In this new approach, mRNA molecules that contain instructions for making a key protein of a pathogen are introduced into the human body. Cells that take up the mRNA start to produce the pathogen’s protein. This lasts only for a short time, because the mRNA is soon degraded. The mRNA and its resulting protein do not make a person ill, but are sufficient to train the immune system to recognise and destroy the pathogen. Interestingly, this method can be used to gain immunity not only to bacterial and viral infections, but also to certain types of cancer.

Delivering the mRNA into cells is challenging. If pure mRNA was injected into the body, it would be immediately degraded before it could even be taken up by cells. To protect the precious mRNA from damage, scientists develop ways to package it into tiny particles, known as nanoparticles, and deliver it into cells.

The left side of the image presents the composition of lipid nanoparticles including names and formulas of the molecules: PolySarcosine, Polyethyleneglycol-Dimyristoyl glycerol (PEG-DMG), 1,2-Dioleyloxy-3-dimethylaminopropane (DODMA), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and Cholesterol. RNA is listed separately as the molecule that is carried by the lipid nanoparticle. On the right side, a model of a lipid nanoparticle shows the arrangement of the molecules. Lipid molecules form a sphere with PolySarcosine-lipid molecules form a shell on the surface of the particle into which RNA is embedded surrounded by lipids.
Lipid nanoparticles (LNP) are tiny particles (less than 100n diameter) made of lipids, which are used in the biotechnology industry to deliver molecules, such as RNA, to cells. Polyethyleneglycol-Dimyristoyl glycerol (PEG-DMG), 1,2-Dioleyloxy-3-dimethylaminopropane (DODMA), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Cristina Sala/BioNTech

To analyse the molecular structure of nanoparticles carrying mRNA, BioNTech used the EMBL Hamburg’s beamline P12 dedicated to small-angle X-ray scattering (SAXS), a technique that allows studying the molecular structure of particles directly in solution. This helped BioNTech to study the structure, efficiency, and behaviour of nanoparticles made of lipids, or a combination of lipids and biopolymers, under different conditions. This will enable the researchers to understand what makes some nanoparticles perform better than others, and to adapt them to desired applications. This could include, for example, modifying the release of mRNA in the cell or adjusting the nanoparticles to be more suitable for certain cell types.

Although the mRNA-based technology is very new and its long-term efficacy still needs to be tested, it has great potential to enable rapid development of vaccines and treatments for various diseases in future. This work also shows the importance of collaboration between industry and research facilities such as those at EMBL, to drive progress and innovation in technology and medicine.

Tags: beamline, biotechnology, Collaboration, EMBL Hamburg, Hamburg, Industry, nanobiotechnology, RNA, SAXS, Structural Biology, Svergun

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