Recombinant promoters and vectors for protein expression in liver and use thereof
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.
1. An isolated nucleic acid molecule, comprising a nucleotide sequence at least 90% identical to any one of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 125, SEQ ID NO: 2, or SEQ ID NO: 126.
2. The isolated nucleic acid molecule of claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 2.
3. The isolated nucleic acid molecule of claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 11.
4. The isolated nucleic acid molecule of claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 12.
5. The isolated nucleic acid molecule of claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 125.
6. The isolated nucleic acid molecule of claim 1 , comprising the nucleotide sequence set forth as SEQ ID NO: 126.
7. A vector comprising the recombinant nucleic acid molecule of claim 1 .
8. The vector of claim 7 , wherein the vector is a viral vector.
9. The vector of claim 8 , wherein the viral vector is an AAV vector.
10. The vector of claim 7 , wherein the viral vector is a gamma-retroviral vector, a lentiviral vector, or an adenoviral vector.
11. A composition comprising the vector of claim 7 in a pharmaceutically acceptable carrier.
12. 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 7 .
13. A method of treating a subject with hemophilia A, comprising selecting a subject with hemophilia A and administering to the subject a therapeutically effective amount of the vector of claim 7 .
14. The isolated nucleic acid molecule of claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 11.
15. The isolated nucleic acid molecule of claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 12.
16. The isolated nucleic acid molecule of claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 125.
17. The isolated nucleic acid molecule of claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 2.
18. The isolated nucleic acid molecule of claim 1 , comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 126.