title: A promising genetic approach to the treatment of beta-thalassemia.
abstract: 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.
authors.affiliation: Laboratory of Gene Transfer and Gene Expression, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. mayc@mskcc.org
authors.forename: C
authors.initials: C
authors.lastname: May
authors.forename: M
authors.initials: M
authors.lastname: Sadelain
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005914:Globins / Q000235:genetics; D006801:Humans; D051379:Mice; D017086:beta-Thalassemia / Q000235:genetics* / Q000628:therapy*
chemical_list: D005914:Globins