The RNA editing enzymes; ADARs convert adenosine to inosine in dsRNA. When ADAR1 is deleted this activates an innate immune response as the unedited dsRNA binds to the innate immune dsRNA receptors. ADAR1 was one of the top hits in a deletion screen to find proteins that would augments anti-PD-1 therapy for cancer. Currently, there is great interest in generating inhibitors specific for ADAR1 that do not effect ADAR2 as it is required for correct functioning of the nervous system. Thus, we propose to generate reporter cell lines with stably integrated ADAR1 and ADAR2 that can be used for high throughput screening of inhibitors. In addition, we will also generate both a positive and negative control cell line. These cell lines will be more sensitive than those that are currently available. We propose to validate these cell lines with a known inhibitor of ADAR. In addition, in collaboration with our colleagues in the Katholieke Universiteit Leuven Belgium we propose to test FDA approved drugs as well as 300,000 compounds on these cell lines.

Sustainable Development Goals

Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.