prof. Koen Raemdonck (PhD)
The therapeutic value of nucleic acid therapeutics for cancer therapy has long been recognized. Nucleic acid drugs generally require delivery into the cytosol of cells to be functional. Unfortunately, the cell membrane is impermeable for hydrophilic macromolecules and cellular delivery is typically facilitated by loading them into nanoparticles. Such particles gain access to cells via endocytosis. However, drug release from endocytic organelles remains a rare event and the internalized carrier and cargo are mainly trafficked toward lysosomes for degradation.
A major aim in our research is therefore to develop innovative nanoparticle-oriented strategies to stimulate cytosolic delivery of nucleic acids (siRNA/mRNA/pDNA), e.g. in cancer-related cell types, both for ex vivo and in vivo applications. To reach this goal, we focus on (1) improving nanoparticle design, (2) repurposing small molecules as delivery-promoting adjuvants and (3) exploiting endogenous materials for nucleic acid delivery (e.g. endogenous lipids and proteins). Importantly, in these projects we aim to fundamentally understand the biological pathways that affect nucleic acid drug delivery in vitro, ex vivo and in vivo to guide the rational design of next generation nanoformulations with optimized intracellular drug delivery properties.
Examples of currently ongoing projects include the optimization and application of nanotechnologies for ex vivo cell engineering in adoptive cell therapy as well as drug combination therapy through concurrent application of small molecules and nucleic acid drugs in a single nanoparticle design.
Koen Raemdonck earned his PhD in Pharmaceutical Sciences in 2009 under the supervision of Prof. Stefaan De Smedt in the lab of General Biochemistry and Physical Pharmacy and continued his research as a postdoctoral fellow of the Research Foundation – Flanders (FWO). He was appointed tenure track professor at the Department of Pharmaceutics, Faculty of Pharmaceutical Sciences of Ghent University in 2016 and was promoted to full professor in 2021. His work is mainly focused on exploring novel bio-inspired approaches for delivery of macromolecular therapeutics across intra-and extracellular biological barriers. He (co-)authored several peer-reviewed publications, many of which in leading journals of the field (Nature Biotechnology, Advanced Materials, ACS Nano, Journal of Controlled Release, Biomaterials), and is (co-)inventor on 6 (pending) patent applications. He received several awards including the biennial National Prize of the Belgian Society of Pharmaceutical Sciences in 2011, the prize of the Royal Academy of Medicine in Belgium for scientific research in Pharmacy 2014 and the T. Nagai Postdoctoral Research Achievement award of the Controlled Release Society in 2016. For his work on delivery of RNA therapeutics, he recently received a prestigious ERC Consolidator Grant in 2020. Koen Raemdonck is a member of various academic societies, including the Controlled Release Society (CRS), where he currently serves as member of the Executive Council of the recently established CRS BeNeLux and France Local Chapter.
- Laure Harinck - doctoral fellow
- A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs, J. Controlled Release 2022, 350: 256-270.
- Surfactant Protein B Promotes Cytosolic SiRNA Delivery by Adopting a Virus-like Mechanism of Action. ACS Nano 2021, 5:8095-8109.
- Photothermal nanofibers enable safe engineering of therapeutic cells, Nat. Nanotechnol., 2021, 16:1281-1291.
- Hydrogel-induced cell membrane disruptions enable direct cytosolic delivery of membrane-impermeable cargo, Advanced Materials 2021, 33:e2008054.
- Cationic Amphiphilic Drugs Boost the Lysosomal Escape of Small Nucleic Acid Therapeutics in a Nanocarrier-Dependent Manner. ACS Nano 2020, 14:4774-4791.
- Pulmonary surfactant and drug delivery: Focusing on the role of surfactant proteins. J. Controlled Release 2018, 291: 116-126.
- Hitchhiking nanoparticles: reversible coupling of lipid-based nanoparticles to cytotoxic T lymphocytes, Biomaterials 2016, 77: 243-254.
- Lessons in simplicity that should shape the future of drug delivery, Nat. Biotechnol. 2015, 33: 1026-1027.