Gene therapy of haematopoietic cells

Gene therapy of haematopoietic stem cells (HSCs) has been under investigation for 15 years. HSCs can be easily transduced with retroviral vectors (Moloney murine leukaemia virus = MMLV) in the mouse and expression of transferred genes can be achieved in long-term reconstituted mice. While human haematopoietic progenitor cells can be transduced with high efficiency using amphotropic MMLV retroviral vectors, and expression of the transferred gene is easily obtained in their progeny cells, it has proven problematic to transfer genes efficiently into the HSCs of humans in clinical trials. Efforts are now under way, in many laboratories, to increase the gene transfer efficiency of retroviral vectors, or alternatively, to develop new vectors that can transduce quiescent human HSCs with higher efficiency than is currently possible. This brief review will address the two main research areas that are being explored. Firstly, investigations in human haematopoiesis to gain understanding into the molecular and cellular mechanisms that control HSC behaviour in vitro and in vivo. Secondly, development of new vectors that can transfer genes to quiescent human HSCs.