Curing human diseases using gene transfer into human hematopoietic stem cells (HSCs) remains a promising avenue for development. In the November 14 issue of the Journal of Clinical Investigation, two independent studies – the first by Stanton Gerson and colleagues at Case Western University and the second by Hans-Peter Kiem and colleagues at the Fred Hutchinson Cancer Research Center – have accomplished, for the first time, the selection and expansion of gene-corrected HSCs from large animals (dogs and humans), using a novel drug-resistance gene, MGMT.
Highly efficient transfer and expression of MGMT into relatively few HSCs using a lentivirus vector led to repopulation of the hematopoietic compartment with gene-corrected cells following suitable drug treatment. This selection system may be useful in human clinical trials of gene therapy in bone marrow transplantation settings.
In an accompanying commentary, Arthur Bank from Columbia University College of Physicians and Surgeons discusses the potential of these results in significantly advancing our knowledge and ability to perform human HSC gene therapy.
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