Delta-erythroid kruppel-like factors and methods of use

Abstract

The invention features δ-erythroid krüppel-like factors (δ-EKLFs), and methods of using nucleic acids encoding δ-EKLFs to increase δ-globin gene expression in a cell.

1 . A method of inducing δ-globin gene expression in a cell, said method comprising introducing a nucleic acid encoding a δ-EKLF polypeptide into said cell or into a precursor of said cell.  
     
     
         2 . The method of  claim 1 , wherein said cell is a pluripotent, hematopoietic stem cell.  
     
     
         3 . The method of  claim 1 , wherein said cell is an erythrocyte precursor cell.  
     
     
         4 . The method of  claim 3 , wherein said erythrocyte precursor cell is an erythrocyte burst-forming cell (BFC-E) or an erythrocyte colony-forming cell (CFC-E).  
     
     
         5 . The method of  claim 1 , wherein said cell is an erythrocyte.  
     
     
         6 . The method of  claim 1 , wherein said cell is present in a mammal.  
     
     
         7 . The method of  claim 1 , wherein said cell, or a precursor of said cell, has been removed from a mammal.  
     
     
         8 . The method of  claim 7 , wherein said cell is a hematopoietic stem cell.  
     
     
         9 . The method of  claim 7 , wherein said mammal has a hemoglobinopathy.  
     
     
         10 . The method of  claim 9 , wherein said hemoglobinopathy is selected from the group consisting of sickle cell anemia and P′-thalassemia.  
     
     
         11 . A δ-EKLF polypeptide.  
     
     
         12 . A nucleic acid encoding a δ-EKLF polypeptide.  
     
     
         13 . A cell that contains a nucleic acid encoding a δ-EKLF polypeptide.  
     
     
         14 . The cell of  claim 13 , wherein said cell is a hematopoietic stem cell.  
     
     
         15 . The cell of  claim 13 , wherein said cell is an erythrocyte precursor cell.  
     
     
         16 . A vector containing a nucleic acid encoding a δ-EKLF polypeptide.  
     
     
         17 . The vector of  claim 16 , wherein said vector is an adeno-associated viral (AAV) vector.  
     
     
         18 . The vector of  claim 16 , wherein said vector is a retroviral vector.  
     
     
         19 . A method for identifying a δ-EKLF polypeptide, said method comprising contacting a nucleic acid containing the sequence 5′-TGA AAC CCT-3′ or the sequence 5′-CTA ATG AAA-3′ with a candidate polypeptide that has been modified such that it differs from wild type β-EKLF by at least one amino acid and identifying said polypeptide by its ability to bind to said nucleic acid.  
     
     
         20 . The method of  claim 19 , wherein said amino acid is in a β-EKLF zinc finger that binds DNA.