Olivier de Jong
Olivier de Jong is a tenure track Assistant Professor at the Department of Pharmaceutics, at the Utrecht Institute for Pharmaceutical Sciences (UIPS). He started his studies at Utrecht University, where he obtained his BSc. in Biology (2007), and his MSc. in Biomedical Sciences at the University Medical Center Utrecht (2010). Dr. de Jong attained his PhD at the Department of Nephrology and Hypertension at the University Medical Center Utrecht (2016), where he studied the role of endothelial cell-derived extracellular vesicles (EVs) in angiogenesis, extracellular matrix remodeling, and RNA transfer.
After attaining his PhD, Dr. de Jong worked as a post-doctoral researcher at the Department of Physiology, Anatomy and Genetics at the University of Oxford (2016-2018), where he studied the molecular mechanisms of EV-mediated RNA transfer. Here he developed a CRISPR/Cas-mediated reporter system to study intercellular RNA transfer at single-cell resolution. He then returned to the University Medical Center in Utrecht to further develop this line of research, and to work on novel approaches for EV-mediated delivery of CRISPR/Cas9, at the Nanomedicine Group at CDL Research. In 2019 he was awarded a VENI grant from the Netherlands Organization for Research (NWO-ENW) to study the role of EV-mediated RNA transfer in tumor development.
He joined the Department of Pharmaceutics in 2021 to set up his own research lines to study EV-mediated RNA transfer, and the development of novel strategies for EV-mediated delivery of biotherapeutics.
The research of Olivier de Jong focuses on the biological function and therapeutic potential of EVs. His group's main focus is to study the molecular basis of EV-mediated transfer of biological cargos, to better understand the role of EVs in homeostasis and pathologies, and to apply these findings to design novel RNA(i) and CRISPR/Cas delivery strategies.
1) Extracellular Vesicles in intercellular communication
EVs are a heterogenous population of small lipid membrane vesicles secreted by cells, which play an important role in intercellular communication through the transfer of biological cargos, including proteins and various RNA species. Whereas the functional role of EV-mediated RNA transfer in the context of many biological and pathological processes has been extensively studied, the cellular mechanisms that regulate and facilitate EV-mediated RNA transfer remain to be elucidated. Using the recently developed CRISPR operated stoplight system for functional intercellular RNA exchange (CROSS-FIRE) (De Jong et al, Nat. Commun. 2020), we aim to unravel these mechanisms. This will allow us to better understand the role of EV signaling in pathological processes, such as tumor development in the tumor micro-environment, and to uncover novel approaches for the design of EV-mediated therapeutic strategies.
2) Extracellular Vesicles as delivery vehicles for biotherapeutics
EVs facilitate intercellular communication as natural carriers of various molecules, including RNA and proteins. Over the last decade, EVs have attracted a large interest as drug delivery vehicles, due to their high potential for biocompatibility, tissue targeting, and capability to cross biological barriers such as the blood-brain barrier. Moreover, EV-loaded intraluminal cargo is shielded from proteases and nucleases, as well as opsonization and degradation from the immune system. Additionally, recent studies suggest that EVs show higher rates of cellular uptake and cargo delivery then their synthetic counterparts (Reshke et al, Nat. Biomed. Eng. 2020; Murphy et al, Nano Lett. 2021). As such, EVs show great potential for delivery of biotherapeutics such as RNA(i) and CRISPR/Cas. In this line of research, we focus on development of novel engineering strategies for targeted cargo loading of EV specific subpopulations, regulated cargo release, endosomal escape, and cell-specific targeting using EV-loaded fusion proteins and chemical modifications to improve EV-mediated delivery of biotherapeutics.
3) CRISPR/Cas activity reporter assays
The CRISPR/Cas system is based on a prokaryotic acquired immune response to protect against viral (phage) infections, by targeting specific sequences of the viral genome that have previously infected the prokaryote. Adaptation of this system has led to the development of CRISPR-Cas technologies that, for the first time in history, allow us to edit genetic code, regulate both transcription and translation, and even modify the epigenetic landscape to regulate gene expression, in a robust and scalable manner. As such, CRISPR/Cas technology has enormous therapeutic potential to treat genetic diseases. One of the current challenges for therapeutic application of this technology, is the design of suitable delivery strategies for CRISPR/Cas. To help optimize the design and development of CRISPR/Cas delivery strategies, we focus on the development of highly sensitive reporter systems for various CRISPR/Cas applications.
1. Kooijmans*, S., de Jong*, O. G., & Schiffelers, R. (2021). Exploring interactions between extracellular vesicles and cells for innovative drug delivery system design. Advanced Drug Delivery Reviews. https://doi.org/10.1016/j.addr.2021.03.017
2. de Jong, O. G., Murphy, D. E., Mäger, I., Willms, E., Garcia-Guerra, A., Gitz-Francois, J. J., Lefferts, J., Gupta, D., Steenbeek, S. C., van Rheenen, J., El Andaloussi, S., Schiffelers, R. M., Wood, M. J. A., & Vader, P. (2020). A CRISPR-Cas9-based reporter system for single-cell detection of extracellular vesicle-mediated functional transfer of RNA. Nature Communications, 11(1), 1113. https://doi.org/10.1038/s41467-020-14977-8
3. Murphy, D. E., de Jong, O. G., Evers, M. J. W., Nurazizah, M., Schiffelers, R. M., & Vader, P. (2021). Natural or Synthetic RNA Delivery: A Stoichiometric Comparison of Extracellular Vesicles and Synthetic Nanoparticles. Nano Letters, 21(4), 1888-1895. https://doi.org/10.1021/acs.nanolett.1c00094
4. de Jong*, O. G., Kooijmans*, S. A. A., Murphy, D. E., Jiang, L., Evers, M. J. W., Sluijter, J. P. G., Vader, P., & Schiffelers, R. M. (2019). Drug Delivery with Extracellular Vesicles: From Imagination to Innovation. Accounts of Chemical Research, 52(7), 1761-1770. https://doi.org/10.1021/acs.accounts.9b00109
5. de Jong, O. G., van der Waals, L. M., Kools, F. R. W., Verhaar, M. C., & van Balkom, B. W. M. (2019). Lysyl oxidase-like 2 is a regulator of angiogenesis through modulation of endothelial-to-mesenchymal transition. Journal of Cellular Physiology, 234(7), 10260-10269. https://doi.org/10.1002/jcp.27695
6. Vervoort*, S. J., de Jong*, O. G., Roukens*, M. G., Frederiks*, C. L., Vermeulen, J. F., Lourenço, A. R., Bella, L., Vidakovic, A. T., Sandoval, J. L., Moelans, C., van Amersfoort, M., Dallman, M. J., Bruna, A., Caldas, C., Nieuwenhuis, E., van der Wall, E., Derksen, P., van Diest, P., Verhaar, M. C., ... Coffer, P. J. (2018). Global transcriptional analysis identifies a novel role for SOX4 in tumor-induced angiogenesis. eLife, 7. https://doi.org/10.7554/eLife.27706
- Email: firstname.lastname@example.orgAssistant Professor
- Extracellular Vesicles, Biopharmaceutics, Regenerative Medicine