About
 |
Our aim is to apply genome editing in the mammalian brain by developing delivery techniques, screening for the most suitable Cas enzymes, and using them in mouse models and in human brain tissue, with the potential to translate to clinical developments. We maintain two main lines of research: fundamental investigation of glia-dependent circuit refinement in the developing brain, using genome editing tools to disturb physiological processes or restore pathways affected by neurodevelopmental conditions, as well as developing new tools to deliver genome editors to the brain for translational applications. Using these techniques, we aim to understand the molecular cues for neuron-microglia interactions, synaptic discrimination, and the removal of a subset of synapses during brain maturation. We focus on non-proteinaceous molecules on the synaptic plasma membrane - lipids and glycans - and develop and apply genome editing methods to modulate synaptic pruning pathways. As models, we use genetically modified mice, ex vivo brain tissue cultures, and iPSC-derived brain cells. We supplement them with the secondary use of surgically resected human brain tissue for direct investigations of human neurons and glial cells. To support our need to efficiently deliver genome editors into the brain, we collaborate with local and international partners who focus on viral and non-viral gene delivery tools. We have a facility for packaging adeno-associated virus and herpesviral vectors, and are currently working with international collaborators to include adenoviruses in our toolkit. By applying genome editing tools for monogenic disorders with strong neuropathological phenotypes, we contribute to developing proof-of-principle repair of point mutations to provide invaluable insights into the efficacy and targeted delivery of the therapeutic payloads. We expect the established workflows to serve in the future as a paradigm for the preclinical development of CRISPR therapies for various genetic disorders. |
| |
|
