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A specific signal for improved uptake: Claudia Lotter receives PhD Award in recognition of her work
At the Swiss NanoConvention 2022, the former nanoscience student Claudia Lotter received the PhD Award — sponsored by the Hightech Zentrum Aargau — in recognition of a first-author publication in the European Journal of Pharmaceutics and Biopharmaceutics. Writing in the publication, Claudia describes how lipid nanoparticles developed for gene therapy can be optimized by tweaking the lipid composition.
Initial research into lipid nanoparticles, such as those used in mRNA vaccines against SARS-CoV-2, was aimed primarily at applications in gene therapy. In order to be used as a vaccine and in gene therapy applications, the lipid nanoparticles that package genetic material must achieve effective uptake into host cells. To ensure good uptake, researchers at the Department of Pharmaceutical Sciences of the University of Basel are working to optimize the composition of the lipid envelopes.
Solutions inspired by nature
As is so often the case in nanotechnology, nature provides some ideas as to how this can be accomplished. For example, dying cells use compounds on their surface to tell neighboring cells to absorb their constituents. One such signaling molecule is the phospholipid phosphatidylserine. Whereas this molecule is actively kept inside healthy cells, it appears on the surface of dying cells, where it springs into action. Viruses also have phosphatidylserine molecules on their surface and can therefore enter host cells, which then begin to produce the constituents of the virus.
Inspired by these natural processes, Dr. Tomaž Einfalt (formerly an SNI doctoral student in the teams of Professors Palivan and Huwyler and now a lab head at Novartis) came up with the idea of integrating phosphatidylserine into lipid nanoparticles in order to improve the transport of genetic material into target cells. Claudia Lotter, who studied nanosciences at the University of Basel, subsequently put this approach into practice as part of her master’s thesis. She completed the analyses in the first year of her doctoral dissertation and has now been awarded the Swiss Nanotechnology PhD Award 2022 for the resulting publication in the European Journal of Pharmaceutics and Biopharmaceutics.
Ideal concentration identified
As part of this work, Claudia showed that the integration of phosphatidylserine into the lipid envelope of the nanoparticles can boost the transfer of RNA and DNA in cell cultures by a factor of 10. “The optimum concentration of phosphatidylserine is 2% to 7% with respect to the total lipid concentration,” she explains. “If the concentration of the integrated phosphatidylserine increases, the positive effect on uptake diminishes again.”
Through their work, Claudia and her coauthors were able to show that the incorporation of defined quantities of phosphatidylserine into lipid nanoparticles opens up new approaches to efficient gene therapy that could be expanded to other therapeutic systems.
In her doctoral dissertation, Claudia is now addressing another aspect of gene therapy. Known as “targeting”, this technique aims to place specific markers on the surfaces of nanoparticles so that the particles can only be taken up by very specific cells. “We’re focusing on specific breast cancer cells, which to a large extent possess human epidermal growth factor receptor 2 (HER2),” she says. “If the selective uptake of genetic material from these cancer cells is successful, it may be possible to develop a gene therapy for this form of cancer — in an approach that could be applied to other malignant tumors.”
That possibility remains a long way off, however. Once Claudia has completed her doctoral dissertation, she would like to follow a development of this kind through to completion. “I can certainly see myself contributing to the development of gene therapies in a startup or in industry,” she says.
Her training as a nanoscientist certainly provides her with the ideal background for such a step. In the interdisciplinary nanosciences degree at the University of Basel, she received a broad grounding in the natural sciences and learned to interact with researchers from various disciplines. Now, as part of her doctoral dissertation, she is also gaining the necessary pharmaceutical knowledge.
Claudia feels that her degree was a demanding but very valuable experience. “All of the hard work was worthwhile,” she says in the interview. “The team spirit among the nanoscience students was excellent, and I learned that you don’t have to achieve everything alone — indeed, you can accomplish so much more as a team.”
After her bachelor’s degree, Claudia had thought for a long time about switching to ETH in Zurich, but she ultimately opted for the master’s program in nanosciences with a focus on molecular biology — and she doesn’t regret her decision. After all, she not only learned a great deal during her course of studies but also made some friends for life.
“Nanotechnology is playing an increasingly important role in drug research and development. Claudia Lotter’s project therefore focuses on novel drug carriers that can be used for gene therapy. In the context of her doctoral thesis, Claudia has impressively shown that the lipid compositions of these nanomaterials significantly influence their interaction with biological systems. We are thus able to develop new strategies for gene therapy.”
Professor Jörg Huwyler,
Department of Pharmaceutical
Sciences, University of Basel
Research group Jörg Huwyler
Publication in European Journal of Pharmaceutics and Biopharmaceutics