Lipids Leader: Rasmus Münter, PhD - Lead Research Scientist
In our latest edition of Lipid Leaders, we speak to Rasmus Münter, PhD. Rasmus is a lipid-based nanoparticle and vaccine adjuvant expert based in Denmark for Croda Pharma. Keep reading to learn more about Rasmus’ background, his research on LNPs and thoughts on how RNA vaccines can be improved.
Please tell us about yourself...
My name is Rasmus Münter and I joined Croda Pharma about one year ago. I work as a scientist in the vaccine adjuvant systems R&D department based in Lyngby in Denmark. I live in Hørsholm in Denmark with my wife and our two small kids who are 4 and 2 years old. I have an education in nanoscience from the University of Copenhagen; a degree combining chemistry, physics and biology. This naturally led me to work with drug delivery, where an understanding of all three disciplines is a great benefit.
Have you always wanted to be a scientist?
Actually no. As a teenager I played bass a lot, and for many years I dreamt of becoming a musician. In high school I was also in the music programme instead of the science programme. The reason I ended up studying nanoscience was not because of a clear vision of what I wanted to do, but just because I thought science was interesting and couldn’t decide between chemistry, physics and biology. I still can’t choose, so I am lucky to work in the vaccine field, where you need to comprehend both physical chemistry, biophysics and immunology.
Tell us about your career path
Before joining Croda Pharma I was at the Technical University of Denmark (DTU) for a long time, both during my PhD, as a postdoc, and later as a scientific consultant. During my academic career, I have worked with different types of lipid-based nanoparticles, both liposomes for delivery of small molecule drugs and lipid nanoparticles for nucleic acid delivery. I have found it particularly interesting how they interact with biological environments (blood proteins, cells and organs) and how they stimulate an immune response. The particles I previously worked with were for delivery of cancer therapeutics or for generation of CAR-T cells in the blood. It wasn’t until I joined the Adjuvant Systems department that I started to deal with the field of vaccines against infectious diseases.
What attracted you to pursue a career at Croda?
I was first attracted to Croda because of their focus on sustainability. I like how the company commits to act responsibly, by trying to enable access of vaccine adjuvant systems to people across the globe. And I am proud to be part of replacing unsustainable products with sustainable ones, such as replacing animal-derived products with products grown in yeast, or replacing molecules harvested from trees in South America with equivalents that can be obtained from plant tissue cultures.
Another reason I joined Croda Pharma was because it gave me a chance to work with highly talented colleagues such as our chemists at Avanti Research. I had used their lipids in many research projects and wanted to be part of the journey of developing novel lipids for drug delivery systems and vaccine adjuvants.
What did you find particularly exciting during your research on lipid nanoparticles (LNPs)?
During my PhD I worked a lot on how drug delivery systems are re-modelled after injection: both how proteins and sugars stick to their surface, but also how the particles are disassembled. I find it really cool that LNPs are designed to be disassembled on purpose: they are formulated with a layer of the polymer PEG anchored into the particle surface by a lipid, but this lipid anchor doesn’t stick very well, meaning that the PEG chains “fall off” after injection. This makes it easier for them to enter cells and deliver their cargo. I think this is a very clever design which really amazes me.
Are there any new insights regarding the composition or addition of other components to delivery systems?
I have a feeling that both we at Croda Pharma and our colleagues around the globe gain new insights every single day! It is a very fast-moving field! We have appreciated the inherent inflammatory nature of many LNPs, and how they can act as both delivery system and adjuvant for some diseases (e.g. respiratory infections such as COVID and RSV), but that the immune response is not suitable for fighting all diseases. However, we cannot just add any immunostimulating molecule to our LNPs, as triggering some inflammatory pathways will shut down the protein synthesis. This goes for several of the classical immunomodulators, such as TLR agonists. However, I have come across some interesting projects where non-classical immunomodulators are added to LNPs, as well as some interesting data where some of the delivered RNA is encoding signalling proteins rather than antigen. I am convinced we will see some very interesting approaches tested in clinical trials in the near future.
How do you think RNA vaccines can be further improved?
One of the benefits of RNA vaccines is that they are very quick to develop, because synthesis of RNA is very standardised, irrespective of the encoded protein. When the antigen changes, for example because a virus is mutating, the vaccine can therefore be modified very quickly. We saw that during the COVID-19 pandemic, where the first batch of RNA vaccines was produced less than a month after the sequence of the virus was shared. This benefit – high speed of development – is particularly important for quickly mutating viruses or for personalised cancer vaccines. However, a drawback of the current approach is still that the RNA needs to be encapsulated into the LNP. I am intrigued by approaches where the RNA and delivery vehicle can be mixed bedside, as this would mean that the delivery vehicles could be made beforehand. Potentially, they could be lyophilised and stockpiled, meaning that we would just need to produce the RNA raw material and ship it to the clinics. This would make the process even speedier than the current RNA-LNP approaches!
A good example is the so-called cationic nanoemulsions. They were developed around a decade ago and thus before everyone started working on LNPs. Emulsion adjuvants are already used in influenza vaccines and have been demonstrated to be efficient and safe. They are known to give a broad repertoire of antibodies, which is very important for diseases such as influenza. Emulsions are nanoparticles consisting of an oil – typically squalene – surrounded by a layer of lipids or surfactants. If these lipids are positively charged (cationic), they can bind RNA and be used as delivery vehicles. Squalene is an immunostimulating compound, and cationic nanoemulsions can therefore both work as delivery vehicle and adjuvant for a vaccine.
Such emulsion-based delivery sounds like an interesting new approach for future developments. Is it something Croda Pharma works on?
We offer emulsifiers used in the “shell” of the oil nanoparticle. For example, Tween and Span variants. Within our Avanti Research portfolio, we offer a lot of cationic lipids that can be used to give the nanoparticles a cationic surface charge. We also have Sustainable Squalene in our portfolio, and it is another product we can be very proud of. Traditionally, squalene is sourced from the livers of deep-water sharks. This has a devastating impact on the marine ecosystem. We should protect life in the oceans, not harvest it. Sustainable Squalene offered by Croda Pharma is produced through fermentation and is therefore not only protecting marine ecosystems but also has a low impact on land use. At the same time, it offers a consistent and secure supply chain. From a chemical point of view, it is molecularly identical with shark squalene while being produced without killing a single animal. Our portfolio includes everything needed to prepare cationic nanoemulsions.
Share something we don't know about you...
I love beer! Well, who doesn’t… I also brew my own beer, and I am really geeky about it. I am fascinated by how flavour compounds are extracted from malt and hops, how the brewing procedure brings these forwards, and how the yeast modifies the molecules, turning bitter sugar water into a well-balanced carbonated beverage. Developing a good recipe for making an IPA is a bit like writing a protocol for making nanoparticles! The main difference is that the product tastes better!
If you had to give one piece of advice to someone thinking about pursuing a career in the research field, what would you tell them?
Have fun! If you don’t think that what you work on is truly exciting, it's not really worth spending your time on.
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