Genome editing involves the targeted and engineered insertion, deletion, modification or replacement of DNA in the genome of a living organism. In 2011, Nature Methods selected genome editing as the 2011 Method of the Year. The Program is focused on developing genome editing as the safest and most robust approach to cure genetic diseases, particularly sickle cell disease, thalassemia, primary immunodeficiencies including severe combined immunodeficiency and hemophilia and ultimately other organ systems as well. Genome editing offers the precise modification of the target gene of interest by homologous recombination while leaving the rest of genome unperturbed. Engineered nucleases make a specific DNA double-strand break in the gene of interest. By simultaneously providing a piece of “donor” DNA, the cell’s endogenous homologous recombination machinery repairs the induced double-strand break using the donor DNA as a template. In this way, precise sequence changes can be introduced into the gene. The Program has made important discoveries in advancing the field of genome editing including the first use of genome editing using engineered nucleases in human cells and optimizing the use of the CRISPR/Cas9 system in primary human stem cells. The Program is planning an IND submission for the treatment of patients with sickle cell disease by the transplantation of their autologous HSC, which have been genetically modified to produce normal hemoglobin.
Matthew Porteus received his MD and PhD degrees from Stanford University in 1994 and completed a fellowship in pediatric hematology/oncology at Boston Children’s Hospital/Dana Farber Cancer Institute in 1999. He joined the faculty of the Stanford University School of Medicine in 2010.