Genetic Engineering of Hematopoietic Stem Cells to Improve the Chance for Racial Minorities to Match with allogeneic unrelated Donors. Homo sapiens

Mismatch of HLA adversely impacts the outcome of patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). This translates into the requirement to identify suitable HLA-matched donors which curtails the chances of recipients, especially those from a racial minority, to successfully undergo alloHSCT. We sought to broaden the existing pool of registered unrelated donors based on analysis that eliminating the expression of the HLA-A increases the chance for finding a donor matched at HLA-B, -C, and -DRB1 regardless of patients’ race. This was achieved using artificial zinc finger nucleases to eliminate expression of HLA-A alleles in HSC while demonstrating the ability of these engineered stem cells to reconstitute hematopoiesis. The loss of HLA-A expression decreases the need to recruit large number of donors to match with potential recipients and has particular impact for patients whose HLA repertoire is under-represented in the current donor pool to find an appropriate HLA-matched donor Overall design: Total RNA obtained from Lineage negative CD34 positive hematopoietic stem cells (with or without ex vivo culture) isolated from umbilical cord blood.