Claudio Alter wrote his doctoral thesis at the De- David Jaeger wrote his doctoral thesis at the De- Toshiya Kozai conducted research for his doctoral partment of Pharmaceutical Sciences. He is con- partment of Physics and was employed there as a thesis at the Biozentrum and is now working tinuing his work as a postdoctoral researcher. postdoctoral researcher. there as a postdoctoral researcher. Optimizing gene therapy Combining the bene昀椀ts Dynamic structures ensure In his doctoral thesis, Dr. Claudio Alter of two systems selective transport explored various methods for e昀昀ectively In his doctoral dissertation, Dr. David Jae- In his doctoral thesis, Dr. Toshiya Kozai and safely delivering genetic material into ger developed an optomechanical plat- studied nuclear pore complexes. target cells. This research contributes to form. The resulting interaction between Nuclear pore complexes serve as se- the development of gene therapies for light and mechanical vibrations has var- lective gateways that control the ex- treating or preventing certain diseases. ious potential applications, including in change of biomolecules between the cy- Initially, Alter investigated di昀昀erent highly sensitive sensors or for the gener- toplasm and nucleus in eukaryotic cells. gene delivery strategies, including extra- ation of quantum states. These gateways consist of a cylindrical cellular vesicles, viruses, and lipid nano- The platform is based on an optical structure in the nuclear envelope with a particles (LNPs). He then enhanced the resonator, in which light is re昀氀ected back central channel of about 50 nanometers lipid composition of LNPs, incorporating and forth with the greatest possible fre- in diameter in which spaghetti-like pro- naturally occurring lipids or extracellular quency. Within this resonator, research- teins, known as disordered proteins, act vesicles — systems that facilitate gene ers position a mechanical structure that as a permeability barrier. They selectively delivery in organisms. These novel formu- can produce the vibrating motion. Thanks allow molecules “tagged” with a trans- lations substantially improved the e昀케- to the resonator, the interactions be- port factor to pass through while prevent- cacy and potency of LNPs both in vitro tween light and the mechanical element ing the entry of nonspeci昀椀c molecules. and in vivo. This improvement was pri- are intensi昀椀ed by several orders of mag- In his work, Kozai studied the perme- marily due to enhanced cellular uptake nitude. This setup can be used not only ability barrier of individual nuclear pore and processing in target cells. Further- to accurately measure the movements of complexes of wild-types and certain mu- more, he investigated the behavior and the mechanical structure, but even to tants using a high-speed atomic force mi- e昀케cacy of di昀昀erent LNP formulations in control the structure using light. croscope. This microscope can image bio- animal models. The distribution and cir- Jaeger implemented the optical cavity molecules at a resolution of a few nano- culation observed in zebra昀椀sh larvae pro- using two glass 昀椀bers with mirror-coated meters and, because of its speed, can vide valuable insights into the behavior ends. For the mechanical resonator posi- generate a 昀椀lm that reproduces the dy- of LNPs. tioned between the two 昀椀bers, he used namics of structural changes. Claudio Alter’s research has provided hexagonal boron nitride (hBN) 昀氀akes sus- The results demonstrate that the dis- a deeper understanding of LNPs, paving pended over holes in a silicon nitride ordered proteins in the central channel the way for the future development of membrane. Given the special properties exhibit dynamic fluctuations and, to- e昀昀ective and potent gene therapies based of the two-dimensional hBN, the resona- gether with various transport factors, on lipid nanoparticles. tor absorbs only a small amount of light form a highly dynamic structure. They Video: https://youtu.be/xR6OzF1z6Sg and ensures long-lasting mirroring. play a crucial role in the functionality of Media release: https://bit.ly/49GHfcf Publication: https://bit.ly/3RM2tiF the barrier and ensure a fast and adaptive Publication: https://bit.ly/3Ny0QT6 response. Publication: https://bit.ly/3S2iMXw SNI Annual Report 2023 17