Year 3

The goal of this project was to develop new technologies to improve the way that hematopoietic stem cells, or HSC, can be genetically modified to treat certain diseases. HSC are the adult stem cells found in the bone marrow that give rise to all of the components of the blood and immune systems. Gene therapy describes ways in which these cells can be modified to provide a treatment for certain genetic diseases, such as sickle cell disease or severe immune deficiencies, as well as serious infections such as HIV/AIDS. Gene editing is a very precise type of gene therapy that involves specific genes being targeted for manipulation, and another goal of this project was to develop ways to use gene editing to block HIV replication. Currently, any type of HSC gene therapy or gene editing needs to be done outside the body, and the process involves harvesting the cells from a patient, manipulating them in a lab, and then returning them to a patient. A much simpler approach would be if we could engineer the HSC while still inside the body, in the bone marrow itself. Towards that goal we have now identified a novel form of a common virus, called AAV, that can seek out HSC in vivo. The overall goal is to use this novel AAV vector to deliver gene editing reagents directly to HSC, and thereby simplify the whole process. Finally, although our initial aim is to combine this novel AAV vector system with gene editing technologies to develop new treatments for HIV, the capability to do in vivo gene editing could also be broadly applied to other diseases of the blood and immune systems.