Recombinant promoters and vectors for protein expression in liver and use thereof

Abstract

Disclosed herein are recombinant viral vectors comprising a liver specific promotor in operable combination with a heterologous nucleic acid sequence encoding a protein, such as a clotting factor. Methods of treating a subject with a clotting disorder, such as hemophilia A or hemophilia B, are also provided.

We claim: 
     
         1 . An isolated nucleic acid molecule, comprising a nucleotide sequence at least 90% identical to any one of SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 124, or SEQ ID NO: 127. 
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 8. 
     
     
         3 . The isolated nucleic acid molecule of  claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 9. 
     
     
         4 . The isolated nucleic acid molecule of  claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 10. 
     
     
         5 . The isolated nucleic acid molecule of  claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 124. 
     
     
         6 . The isolated nucleic acid molecule of  claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 127. 
     
     
         7 . The isolated nucleic acid molecule of  claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 8. 
     
     
         8 . The isolated nucleic acid molecule of  claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 9. 
     
     
         9 . The isolated nucleic acid molecule of  claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 10. 
     
     
         10 . The isolated nucleic acid molecule of  claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 124. 
     
     
         11 . The isolated nucleic acid molecule of  claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 127. 
     
     
         12 . A vector comprising the recombinant nucleic acid molecule of  claim 1 . 
     
     
         13 . The vector of  claim 12 , wherein the vector is a viral vector. 
     
     
         14 . The vector of  claim 13 , wherein the viral vector is an AAV vector. 
     
     
         15 . The vector of  claim 12 , wherein the viral vector is a gamma-retroviral vector, a lentiviral vector, or an adenoviral vector. 
     
     
         16 . A composition comprising the vector of  claim 12  in a pharmaceutically acceptable carrier. 
     
     
         17 . A method of inducing blood clotting in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the vector of  claim 12 . 
     
     
         18 . A method of treating a subject with hemophilia B, comprising selecting a subject with hemophilia B and administering to the subject a therapeutically effective amount of the vector of  claim 12 .