CRISPR-Cas9 Mediated Manipulation of Epilepsy- associated Genes and its Possible Application in Mouse and Human Organotypic Hippocampal Slice Cultures

Despina Tsortouktzidis1, Albert Becker1, Susanne Schoch1, Karen van Loo1, Henner Koch2

1 Section for Translational Epilepsy Research, Department of Neuropathology, University of Bonn Medical Center
2 Department of Neurology, University Hospital RWTH Aachen

Precise genome editing in combination with viral delivery systems provides a valuable tool for neuroscience research. The CRISPRa/i (activation/inhibition) system is a powerful technique for specific manipulation of promoters and can be used to switch On and Off endogenous gene expression. Viral delivery of the CRISPRa/i system in mouse and human hippocampal organotypic slices could constitute a valuable approach to precisely study the role of potential pathogenic genes and to confirm the results in a human scenario.  Here, we develop a CRISPRa/i system to target the promoter of the epileptogenesis associated gene encoding the T-Type calcium channel Cav3.2.