One of the IGI’s longer-term projects is to deliver gene editing biomolecules to hard-to-reach cells in the human body. Fortunately, we can already edit certain types of cells, letting us make a difference for patients sooner. Ex vivo genome editing involves removing stem cells from a patient’s blood, correcting a deleterious mutation, and reintroducing the edited cells. Our strategy maximizes editing of disease-causing mutations to produce a large population of corrected hematopoietic stem cells that could be re-engrafted into patients. This powerful approach can be applied to a range of blood disorders, including severe combined immunodeficiency and beta-thalassemia.
Our first efforts focus on sickle cell disease. This recessive genetic disorder causes hemoglobin molecules to stick together, deforming red blood cells into a characteristic “sickle” shape that leads to blood vessel blockages. This painful condition primarily afflicts those of African ancestry, affecting hundreds of thousands of people worldwide. We are actively working to improve our ex vivo editing system, perform large-scale mouse studies, and initiate an early phase clinical trial to test CRISPR-Cas9 as a new treatment for sickle cell disease.
Selection-free Genome Editing of the Sickle Mutation in Human Adult Hematopoietic Stem/Progenitor Cells.
DeWitt MA, Magis W, Bray NL, Wang T, Berman JR, Urbinati F, Heo S, Mitros T, Muñoz DP, Boffelli D, Kohn DB, Walters MC, Carroll D, Martin DK, and Corn JE. Science Translational Medicine (2016).