Epigenome Editing for Gene Therapy, Cell Programming, and Functional Epigenetics

The advent of genome engineering technologies, including the RNA-guided CRISPR/Cas9 system, has enabled the precise editing and regulation of endogenous human genes and epigenetic states. We have applied these tools to the correction of mutations that cause genetic disease and also adapted them to manipulate the epigenome and control cell fate decisions. For example, we have engineered CRISPR/Cas9-based tools to regulate the expression of endogenous genes and applied these tools to control diverse genes relevant to disease, development, and differentiation. Genome-wide analysis of the DNA-binding, gene regulation, and chromatin remodeling by these targeted epigenome modifiers has demonstrated their exceptional specificity. We have recently applied these technologies to control the decisions of stem cells to become specific cell fates and reprogram cell types into other lineages for drug screening and disease modeling. We have used in vivo epigenome editing to alter expression of genes associated with complex disease phenotypes. Genome-wide screens of epigenetic modulation of target gene expression has enabled the discovery of novel distal regulators of target gene expression. Collectively, these studies demonstrate the potential of modern genome engineering technologies to capitalize on the products of the Genomic Revolution and transform medicine, science, and biotechnology.