Adeno-associated virus mediated delivery of C1E1 as a therapy for angioedema
This invention is directed to a vector which comprises a promoter operably linked to a nucleic acid sequence encoding the human C1 esterase inhibitor or Factor XII. The invention is also directed to a composition comprising the vector and a method of using the vector to treat or prevent hereditary angioedema.
1. A method of treating a deficiency in a functional plasma C1 esterase inhibitor in a mammal, or treating or preventing any symptom thereof, comprising administering a recombinant adeno-associated virus (AAV) vector comprising a promoter operably linked to a nucleic acid sequence that encodes human C1 esterase inhibitor (C1EI) to the mammal, whereupon the nucleic acid is expressed to produce a protein.
2. The method of claim 1 , wherein the mammal has hereditary angioedema.
3. The method of claim 2 , wherein the method inhibits or reduces submucosal or subcutaneous edema in the mammal.
4. The method of any of claim 3 , wherein the composition is administered to the mammal once before and/or after onset of edema.
5. The method of any of claim 3 , wherein the composition is administered to the mammal two or more times before and/or after onset of edema.
6. The method of claim 1 , wherein the mammal is a human.
7. The method of claim 1 , wherein the composition is administered to the mammal by a route of administration selected from the group consisting of intraoral, intramuscular, transdermal, intravenous, intraarterial, subcutaneous, intradermal, and intraperitoneal.
8. The method of claim 1 , wherein the AAV vector is a non-human adeno-associated virus.
9. The method of claim 8 , wherein the non-human adeno-associated virus is a rhesus macaque adeno-associated virus.
10. The method of claim 9 , wherein the rhesus macaque adeno-associated virus is the adeno-associated virus serotype rh.10.
11. The method of claim 1 , wherein the promoter is a constitutively active promoter.
12. The method of claim 1 , wherein the promoter is a chicken beta-actin promoter.
13. The method of claim 12 , wherein the vector further comprises a cytomegalovirus (CMV) enhancer sequence.
14. The method of claim 13 , wherein the nucleic acid sequence that encodes human C1EI encodes a polypeptide comprising the amino acid sequence of SEQ ID NO: 1.