The investigators have discovered and cloned a patentable transcription factor, BP2, which they believe suggests a totally new therapeutic approach to the treatment of sickle cell anemia. BP2 is a repressor of the adult b-globin gene, and they expect that overexpression of BP2 will both decrease expression of bs and increase expression of fetal genes. Based on clinical observations, this should ameliorate the manifestations of sickle cell anemia. BP2 also binds near the other adults globin gene, d, the fetal g genes, and to the promoter of a gene implicated in leukemia. BP2 therefore may play a significant role in regulation of fetal and adult globin genes, in hemoglobin switching, and in leukemia. Therefore, BP2 may be of significant interest to other investigators interested in hemoglobinopathies and leukemia.
The specific aims of this proposal are to: (1) verify the authenticity of the BP2 clone, (2) express BP2 cDNA, and (3) determine whether exogenous BP2 represses the b-globin gene in cultured cells. The long term goals are to determine the feasibility of gene therapy of sickle cell anemia using cloned BP2 cDNA and to produce molecular reagents for use by other investigators interested in hemoglobinopathies and leukemia.
