The medical community is on the cusp of revolutionary curative treatments through therapeutic genome editing. However, technical limitations, such as unintentional and unpredictable gene silencing, along with lengthy development and regulatory approval processes severely restrict the scope of these therapies. Recent advancements that we and others have made in the field of precision genome editing offer potential solutions for overcoming barriers to translating genome editors into genome therapeutics. In this work I demonstrate novel applications of precision genome editing tools that could provide more immediate benefit to ailing populations. I explore multiple gene editing modalities and describe a flexible approach for rapidly producing gene editors as ribonucleoproteins. Using prime editing, I introduce epilepsy variants from individual patients into wild type mice. We validate the precision of in vivo genome editing using both Next-Generation Sequencing and electrophysiology. Notably, a portion of wild type mice edited with these ultra-rare epilepsy variants display spontaneous motor seizures, reproducing a key clinical symptom of the modeled patient. I further demonstrate how these mice could be used as surrogate models to test pharmacotherapies in the context of an individual’s specific genetic variants, providing direct evidence for new applications of prime editing in precision medicine. This approach is robust across multiple genomic loci and produces reliable models of genetic epilepsies much faster than traditional disease modeling. Overall, these results are among the first to show successful application of prime editing in the brain, among the first to demonstrate the production of prime editing ribonucleoproteins, and demonstrates a novel application of these technologies that can directly benefit patients with genetic epilepsies.