Sangamo BioSciences Inc has been awarded a $1 million NIH grant to conduct research on the application of Sangamo's zinc finger DNA binding transcription factor (ZFP TF) technology in the development of a treatment for sickle cell disease in collaboration with researchers at the University of Alabama, Birmingham (UAB).

The grant entitled "Transactivation of Fetal Hemoglobin Genes for the Treatment of Sickle Cell Disease" was awarded by the National Heart, Lung and Blood Institute and will be paid out over a 4-year period.

Investigators at Sangamo and UAB will work collaboratively to target fetal hemoglobin genes with engineered ZFP TFs. These proteins will then be tested in a mouse model of human sickle cell disease developed by the principal investigator of the grant, Dr. Tim Townes, professor of biochemistry and molecular genetics and chairman of the same department at UAB, and his colleagues.

Sickle cell disease is caused by a mutation in the adult human b-globin gene that alters the solubility of hemoglobin under certain physiological conditions. The ensuing disease is characterized by chronic hemolytic anemia with episodes of severe pain and tissue damage that often result in kidney failure, liver disease, stroke and other complications. According to the National Heart, Lung and Blood Institute of the National Institutes of Health, approximately 72,000 people in the U.S. have sickle cell disease. Approximately 2.5 million Americans carry the sickle cell trait. Although sickle cell disease was the first disease to be understood at the molecular level there is still no adequate long-term treatment or cure. Normally during development, genes encoding fetal hemoglobin are switched off and the body begins to express adult globin genes and produce adult hemoglobin. It is known that individuals that have the sickle cell mutation in their adult hemoglobin gene but continue to express moderate levels of fetal hemoglobin do not have symptoms of sickle cell disease.

Zinc finger DNA-binding proteins are the dominant class of naturally occurring transcription factors in organisms from yeast to humans. Transcription factors bind to DNA to regulate gene expression. Transcription factors made from ZFPs (ZFP TFs) allow precise targeting to a particular gene or genes of interest. Since the over-expression or under-expression of individual genes is the basis for many diseases, the ability to regulate genes with engineered ZFP TFs has significant potential therapeutic benefit.