Science has advanced knowledge on genes by deleting them in model organisms and by mapping gene mutations in human diseases. However, the ability to enhance gene expression in cells where it is normally expressed is currently limited. This is critical in finding cure for neurodegenerative diseases because expression of a gene in wrong cells in the brain can lead to severe side effects. I have shown that it is possible to enhance gene expression precisely in naturally expressing cells using DNA editing. However, current DNA editing is inefficient and irreversible, limiting its applicability. Here I propose new technology which allows to reversibly enhance or inhibit gene expression without a need for DNA editing. I also propose a screen which would substantially simplify DNA editing based enhancement of gene expression, broadening its applications. Finally, I propose testing of the treatment potential of the new tools in mouse models of Parkinson's disease and Alzheimer's disease.

2022

2026