Poster #079
Regulating Gene Expression in Neurons with CRISPR Epigenome Editing
Mentors: Peter Colias, Da Zu, PhD and James Nuñez, PhD
Epigenome editing has emerged as a powerful tool for modulating gene expression without altering the DNA sequence. CRISPRoff, a system that employs a catalytically inactive Cas9 protein (dCas9) fused to chromatin effector domains, enables targeted gene silencing through epigenetic modifications. In this study, we delivered the CRISPRoff and single guide RNA (sgRNA) complexes into induced pluripotent stem cell (iPSC)-derived neurons using virus-like particles (VLPs), aiming to silence the tau gene, which is linked to numerous neurodegenerative diseases. Following treatment, we employed nanopore sequencing to profile DNA methylation at the tau locus and assess epigenetic changes induced by CRISPRoff. By modulating epigenetic marks such as DNA methylation, this method advances our ability to reprogram the epigenome in neurons, holding great potential for both basic research and therapeutic interventions in neurological disorders.