Two main roadblocks stand between us and the realization of genomic editing-based treatments for genetic disease: the lack of a system for delivering editing tools to disease-affected cells and inefficient gene replacement. We are currently unable to efficiently and precisely deliver editing molecules into the parts of the body that are harmed by genetic mutations. We have the tools, but can't quite get them where they need to go. We are investigating various approaches to delivering CRISPR-Cas9 components into specific cells, tissues, and organs.
Furthermore, replacing a faulty gene with a healthy copy requires Cas9 to cut a particular DNA site and for the cell to repair the break in a manner that doesn't typically occur very frequently. Thus, developing methods to enhance the efficiency of this repair pathway is critical for eventually treating human genetic disease. We study the steps that follow DNA cleavage by Cas9 to gain insight into how different repair pathways are initiated and how we might better control this process.
Critically, technological advancements in delivery and gene replacement will not only benefit humans directly; they will also improve genomic engineering of plants, livestock, and microbes.
Non-homologous DNA increases gene disruption efficiency by altering DNA repair outcomes.
Richardson CD, Ray GJ, Bray NL, and Corn JE. Nature Communications (2016).
Enhancing homology-directed genome editing by catalytically active and inactive CRISPR-Cas9 using asymmetric donor DNA.
Richardson CD, Ray GJ, DeWitt MA, Curie GL, and Corn JE. Nature Biotechnology (2015).