The ZonMW off road subsidy is meant to give young researchers the opportunity to test their groundbreaking hypothesis and to develop this innovative idea into a proof of concept. Applications should be characterized by their high-risk profile and unconventional research methods ('high risk, high gain' projects). Specifically, the research should be fundamental (pilot data are not needed), in the field of (bio)medical of health sciences and concerns the development of technologies for a durable health system.
This year ZonMW granted two RIMLS researchers an off road subsdy:
Title: Aptamer technology for targeted siRNA delivery to dismantle the immunosuppressive tumor micro-environment
Despite initial success of cancer therapies, many patients develop progressive disease and eventually die. Although tumor-reactive immune responses are observed, these often fail to eliminate the tumor as the tumor cells create a suppressive micro-environment. Hereto, they secrete immunosuppressive factors, recruit suppressive antigen-presenting cells and utilize inhibitory signaling pathways. The aim of my project is to develop innovative CLEC12A-directed aptamer technology to selectively deliver silencing RNAs (siRNA) in myeloid tumor cells and suppressive antigen-presenting cells. Thereby, multiple immune escape mechanisms can be simultaneously silenced with low risk of (severe) toxicity in healthy tissues. By taking down the tumor’s defenses, immune control can be reinvigorated. Eventually, RNA aptamer/siRNA conjugates can be easily manufactured for clinical investigations. Proof-of-concept will pave the way for targeted interference with suppressive mechanisms in numerous cancers.
Patrick Jansen, Dept. of Dermatology, theme Infectious diseases and global health
Title: Antimalarials as a source of new anti-psoriatic drugs: adverse effects create opportunities
Psoriasis is a common skin disease with red inflamed patches and excessive scaling, which is caused by rapidly dividing skin cells. Patients with mild to moderate psoriasis can be treated topically with steroids or vitamin D3, but the use of these drugs is limited by lack of efficacy or side effects. Safe and effective topical agents are therefore an unmet medical need. In search for new drugs against the malaria parasite we tested novel compounds for undesirable side effects on human cells. Quite unexpectedly some of these compounds were found to slow down cell division of skin cells without being toxic. These compounds might be beneficial in an ointment to reduce the excessive scaling in psoriasis patients. This is what Patrick Jansen will investigate in the granted ZonMW Off-road project.
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