Hematopoietic stem cell gene therapy: selecting only the best.
Hematopoietic stem cell (HSC) gene therapy can potentially cure a variety of human hematopoietic diseases, such as sickle cell disease. Selection and expansion of gene-corrected HSCs has now been accomplished for the first time using HSC from large animals - dogs and humans - with a novel drug-resistance gene, MGMT, which is not expressed in normal HSCs (see the related articles beginning on pages 1561 and 1581). Highly efficient lentiviral transfer and expression of MGMT into relatively few HSCs led to repopulation of most of the hematopoietic compartment with gene-corrected cells following suitable drug treatment. This selection system may be useful in human clinical trials to permit gene therapy in autologous and allogeneic bone marrow transplantation settings.
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Arthur
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Departments of Medicine and of Genetics & Development, Columbia University College of Physicians and Surgeons, Armand Hammer Health Science Center, New York, New York 10032, USA. ab13@columbia.edu
D000818:Animals; D004285:Dogs; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D016086:Lentivirus / Q000235:genetics