Adeno-associated virus factor VIII vectors
View Patent ↗The invention provides improved adeno-associated virus (AAV) Factor VIII (FVIII) vectors, including AAV FVIII vectors that produce a functional Factor VIII polypeptide and AAV FVIII vectors with high expression activity.
1. An adeno-associated virus (AAV) vector, comprising an AAV2 5′ inverted terminal repeat (ITR), a liver specific transcriptional regulatory region, a functionally active FVIII coding region, a polyadenylation sequence, an AAV2 3′ ITR, and optionally one or more introns, wherein the functionally active FVIII coding region comprises nucleotides 923-5296 of SEQ ID NO: 9.
2. A method of producing a recombinant adeno-associated virus (AAV) particle comprising
A) culturing a cell that has been transfected with an AAV vector of claim 1 ; and
B) recovering recombinant AAV particle from the supernatant of the transfected cell.
3. A viral particle comprising an AAV vector of claim 1 .
4. A method of treating a patient suffering from hemophilia A comprising intravenously administering to the patient an effective amount of an AAV vector of claim 1 .
5. A composition comprising an AAV vector of claim 1 for the treatment of hemophilia A.
6. An isolated nucleic acid encoding a functionally active FVIII protein, said isolated nucleic acid comprising nucleotides 923-5296 of SEQ ID NO:9.
7. An adeno-associated virus (AAV) vector comprising the nucleotide sequence of SEQ ID NO: 1.
8. A viral particle comprising an AAV vector of claim 7 .
9. A method of treating a patient suffering from hemophilia A comprising intravenously administering to the patient an effective amount of an AAV vector of claim 7 .