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Annals of the New York Academy of Sciences 850:151-162 (1998)
© 1998 New York Academy of Sciences

Retroviral Vectors Aimed at the Gene Therapy of Human ß-Globin Gene Disorders^a

We are focusing on the development of complex retroviral vectors containing human ß-globin gene and ß-LCR for the gene therapy of sickle cell disease and ß-thalassemias. First generation vectors containing mutated splice-sites to insure stability of proviral transfer enabled long-term reconstitution in 10/12 transplanted mice for a least 8 months with high expression levels in 2 out of 3 mice analyzed (5% and 20% murine ß). Transfer and expression were also achieved in secondary recipients (range: 3-11% murine ß). Position independent expression was not observed. In an effort to increase the efficiency of gene transfer and obtain complete reconstitution of recipient mice with exclusively transduced cells while enriching for proviral integration into active chromatin regions, we have incorporated a cassette expressing CD24 or the green fluorescent protein (GFP). Stable transfer to murine bone marrow cells allowed efficient FACS-sorting of pure populations of transduced cells. A family of vectors based on these principles and containing segments of - or -globin genes were also designed for systematic analysis of their anti-sickling properties.