Stijn Hofstraat
TU Eindhoven
Stijn Hofstraat (1996) completed his bachelor’s and master’s program Biomedical Engineering at the Eindhoven University of Technology. His master thesis focused on controlled drug release via nanoparticles and biomaterials, a joint collaborative project between prof. Patricia Dankers and prof. Jan van Hest. During a 6-month internship, he researched the ex-vivo activation and expansion of T cells in David Mooney’s lab at the Harvard John A. Paulson School of Engineering and Applied sciences. After graduating, he joined the Mulder Lab as a PhD student in Eindhoven where he develops RNA-based nanotherapeutics.
Presentation: Apolipoprotein-based delivery platform for gene silencing in hematopoietic stem and progenitor cells
Over the last decade, targeting the adaptive immune system has been a highly successful immunotherapy approach. Similarly, modulating the innate immune system holds great therapeutic potential. Our strategy is to deliver small interfering RNA (siRNA) to the hematopoietic stem and progenitor cells in the bone marrow. Therefore, we have developed a novel RNA delivery platform based on apolipoprotein A1 (ApoA1). ApoA1 acts as a structural stabilizer for lipid-based nanoparticles, and it has inherent affinity for myeloid cells and their progenitors. Using ApoA1, siRNA, and fatty molecules, we developed a library of nanoparticles for siRNA delivery, called siRNA-aNPs. The library nanoparticles were screened for physicochemical properties and in vitro silencing. From the library, we selected 6 representative compositions for in vivo evaluation. Using radiolabeling of the siRNA, we identified several siRNA-aNP formulations that preferentially accumulate in the bone marrow. Furthermore, via flow cytometry we demonstrated significantly higher uptake of our lead siRNA-aNP in hematopoietic stem and progenitors cells compared to standard LNPs for siRNA delivery. In future experiments, we will evaluate the silencing efficacy of the lead candidate in vivo. Finally, we will set-up treatment studies in various disease models to show siRNA-aNPs’ full therapeutic potential.
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