Adeno-associated virus mediated delivery of c1ei as a therapy for angioedema

Abstract

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 vector comprising a promoter operably linked to a nucleic acid sequence which encodes human C1 esterase inhibitor (C1EI) or a nucleic acid sequence which encodes human Factor XII, or both. 
     
     
         2 . The vector of  claim 1 , wherein the vector is an adeno-associated virus (AAV), an adenovirus, a lentivirus, a retrovirus, or a plasmid. 
     
     
         3 . The vector of  claim 2 , wherein the vector is an AAV vector. 
     
     
         4 . The vector of  claim 3 , wherein the AAV vector is a non-human adeno-associated virus. 
     
     
         5 . The vector of  claim 4 , wherein the non-human adeno-associated virus is a rhesus macaque adeno-associated virus. 
     
     
         6 . The vector of  claim 5 , wherein the rhesus macaque adeno-associated virus is the adeno-associated virus serotype rh.10. 
     
     
         7 . The vector of  claim 1 , wherein the promoter is a constitutively active promoter. 
     
     
         8 . The vector of  claim 1 , wherein the promoter is a cell type specific promoter. 
     
     
         9 . The vector of  claim 1 , wherein the promoter is an inducible promoter. 
     
     
         10 . The vector of  claim 1 , wherein the promoter is a chicken beta-actin promoter. 
     
     
         11 . The vector of  claim 1 , wherein the vector comprises a nucleic acid sequence which encodes C1EI encodes a polypeptide comprising SEQ ID NO: 1. 
     
     
         12 . The vector of  claim 1 , wherein the vector comprises a nucleic acid sequence which encodes Factor XII encodes a polypeptide comprising SEQ ID NO: 3. 
     
     
         13 . A composition comprising the vector of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         14 .- 21 . (canceled) 
     
     
         22 . A recombinant mouse that models human hereditary angioedema, the recombinant mouse comprising a mutation of SERPING1 that reduces C1EI activity in the mouse as compared to the same type of mouse without the SERPING1 mutation. 
     
     
         23 . The recombinant mouse of  claim 22 , wherein the recombinant mouse comprises a mutation in exon 3 of SERPING1. 
     
     
         24 .- 31 . (canceled)