A promising genetic approach to the treatment of beta-thalassemia.
The stable introduction of a functional gene into autologous stem cells is a potentially powerful approach to treat a number of inherited or acquired diseases. One challenge facing this approach is to express adequate levels of the therapeutic transgene in a regulated and sustained fashion, eventually restricting expression to a single lineage developing from the transduced stem cells. Until now, low-level expression, position effects, and transcriptional silencing have hampered the effectiveness of retroviral-mediated gene transfer. In an effort to overcome these obstacles, we have systematically investigated vectors encoding the human beta-globin gene linked to selected combinations of proximal and distal genetic regulatory elements. Our results demonstrate that with thoughtful vector design one can successfully express long-term, therapeutic levels of virally encoded human beta-globin in the erythroid progeny of hematopoietic stem cells.
May
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Laboratory of Gene Transfer and Gene Expression, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. mayc@mskcc.org
Sadelain
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D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005914:Globins / Q000235:genetics; D006801:Humans; D051379:Mice; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
D005914:Globins