Til bevillingsoversigt

Targeted degradation of oncogenic mRNA with non-enzymatic degraders

Carlsbergfondets internationaliseringsstipendier

What

Certain types of cancer can occur as a result of the dysregulated production of a specific oncogenic protein, which can lead to uncontrolled growth and disease. If the dysregulated protein is a so-called "undruggable" target for conventional therapeutics, alternative strategies are required to treat the disease. In this project, I aim to develop novel molecules that target and degrade the mRNA of such an "undruggable" oncogenic protein, which prevents its translation and results in reduced production of the protein. This approach can potentially attenuate uncontrolled cell growth and give benefits for cancer and tumor treatments.

Why

The oncogenic protein target in this project is involved in a large amount of cancers and has strong implications in tumor growth. Nevertheless, no approved treatment options are available to date and therefore new ways of targeting this protein are highly desirable. The anticipated approach of applying molecules that degrade mRNA chemically through a novel mechanism represents an exciting opportunity to pave the way for new therapeutics and to establish a more general platform that could enable us to target specific proteins in a precise manner as an addition to known biology-based methods.

How

The project will be carried out with Prof. Gonçalo Bernardes at the University of Cambridge. His world-leading chemical biology group has made important contributions in the fields of protein chemistry and bioconjugation, cancer biology, drug release and RNA technology. This research environment represents the ideal combination of chemistry and biology to conduct this ambitious project, which will involve the synthesis and optimization of novel degrader molecules and their evaluation in various cancer models as potential anti-cancer therapeutics.

SSR

Cancer represents one of largest burdens on public health and new ways of targeting important oncogenic proteins are in great need. We envision that the successful outcome of this project could lead to the development of alternative treatment options for cancer patients, who were previously not able to receive treatment. The gained insights from this project into cancer biology and the novel methodology to target a specific oncogenic protein could, on the long term, improve the life of patients and advance our general understanding of cancer development.