A Novel Epigenetic Editing Platform - CRISPR-based gene editing has become mainstream in its popularity because of its approval as a therapeutic. Yet, concerns about safety persist since CRISPR-based therapeutics result in permeant changes to the DNA sequence, which are irreversible if side effects arise. Epigenetic editing, manipulation the epigenome in a targeted way to alter gene expression, in contrast, has become an interesting alternative since it avoids permanent changes of DNA sequences. However, epigenome editing is an immature field with limited tools available. Options include fusion of epigenetic modifying enzymes to sequence specific DNA targeting proteins such as TALEs and Zinc Fingers or a version of CRISPR that uses an enzymatically dead Cas protein. All of these approaches have limitations including, difficulty in design with extensive cloning effort, variability in binding affinity, off-target editing and delivery challenges based on the large size of the targeting proteins. In this proposal we describe a new epigenetic editing platform that uses a completely novel targeting approach for recruitment of epigenetic effectors to specific genomic loci resulting in targeted alterations to the epigenetic landscape and directed changes in gene expression. This platform will initially be developed as a research use only tool but, in the long term, has the potential for use in a therapeutic setting.
