Genome and Epigenome Editing for Gene Therapy, Cell Programming, and Functional Genomics

Charles A. Gersbach

Rooney Family Associate Professor

Department of Biomedical Engineering – Duke University


Seminar Information

Seminar Date
November 17, 2017 - 2:00 PM

Location
The FUNG Auditorium


Abstract

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 engineered CRISPR/Cas9-based nucleases to correct the human dystrophin gene that is mutated in Duchenne muscular dystrophy patients. When we delivered these nucleases to cells from patients with this disease, the correct gene reading frame and expression of the functional dystrophin protein were restored in vitro and following cell transplantation into mouse models in vivo. When delivered directly to a mouse model of this disease, gene editing by the CRISPR/Cas9 system led to gene restoration and improvement of biochemical and mechanical muscle function. More recently, we have developed and tested a novel humanized mouse model of Duchenne muscular dystrophy for preclinical development of gene editing therapies. In other studies, 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 that could be used for drug screening and disease modeling. Additionally, we are developing epigenome editing tools to annotate the function of the non-coding genome and illuminate the role of gene regulation in disease susceptibility and drug response. 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.

Speaker Bio

Dr. Charles A. Gersbach is the Rooney Family Associate Professor at Duke University in the Departments of Biomedical Engineering and Orthopaedic Surgery, an Investigator in the Duke Center for Genomic and Computational Biology, and Director of the Duke Center for Biomolecular and Tissue Engineering. He received his PhD from the Georgia Institute of Technology and completed postdoctoral training at The Scripps Research Institute.  His research interests are in genome and epigenome editing, gene therapy, regenerative medicine, biomolecular and cellular engineering, synthetic biology, optogenetics, and genomics and epigenomics.  Dr. Gersbach’s laboratory at Duke University is focused on applying molecular and cellular engineering to develop new methods to genetically modify genome sequences and cellular gene networks in a precise and targeted manner.  Dr. Gersbach’s work has been recognized through awards including the NIH Director’s New Innovator Award, the NSF CAREER Award, the Outstanding New Investigator Award from the American Society of Gene and Cell Therapy, the Allen Distinguished Investigator award, and induction as a Fellow of the American Institute for Medical and Biological Engineering.