REDUCING CXCR4 EXPRESSION AND/OR FUNCTION TO ENHANCE ENGRAFTMENT OF HEMATOPOIETIC STEM CELLS

摘要

Provided herein are methods of enhancing engraftment of hematopoietic stem cells (HSC) in recipient subjects by reducing expression (or activity) of CXC chemokine receptor 4 (CXCR4). Such methods can be used in gene therapy protocols and in HSC transplantation, for example allowing this to occur without radiation or chemotherapy conditioning as is typically done in non- myeloablative HSC transplant. In some examples, gene editing methods are used to delete one copy of the CXCR4 gene before HSC or bone marrow transplantation, enhancing the efficiency and durability of donor cell repopulation.