Platelet targeted treatment

Abstract

The present disclosure relates to compositions and methods for targeting expression of exogenous genes to platelets. In particular, the present disclosure relates to treatment of hemophilia and other diseases and conditions by targeting expression of exogenous agents (e.g., clotting factors) to platelets.

1 - 27 . (canceled) 
     
     
         28 . A composition, comprising:
 an expression vector comprising: a) an expression cassette comprising a fragment of the integrin αIIb gene (ITGA2B) promoter; a targeting factor that targets expression of said gene of interest to a cancer cell or a hematopoietic cell lineage producing platelets; and b) an exogenous gene of interest operably linked to said expression cassette, wherein said exogenous gene of interest is an anti-angiogenic agent or an anti-neoplastic agent.   
     
     
         29 . The composition of  claim 28 , wherein said promoter is selected from the group consisting of nucleotides 18-1271 of SEQ ID NO: 21, nucleotides 18-939 of SEQ ID NO:22, and nucleotides 2454-3156 of SEQ ID NO:25. 
     
     
         30 . The composition of  claim 28 , wherein said anti-neoplastic agent is IL-24. 
     
     
         31 . The composition of  claim 28 , wherein said targeting factor is a fragment of the human Von Willebrand Factor propeptide (VWFpp) operably linked to a D2 domain. 
     
     
         32 . The composition of  claim 28 , wherein said vector is a self-inactivating vector. 
     
     
         33 . The composition of  claim 32 , wherein said vector is a retroviral vector. 
     
     
         34 . The composition of  claim 33 , wherein said retroviral vector is a lentiviral vector. 
     
     
         35 . A hematopoietic stem cell or cancer stem cell comprising the composition of  claim 28 . 
     
     
         36 . The stem of cell of  claim 35 , wherein said stem cell is ex vivo. 
     
     
         37 . A method of treating cancer, comprising:
 a) contacting a cancer stem cell or a hematopoietic stem cell with a composition of  claim 28  to generate a modified stem cell under conditions such that said exogenous gene of interest is expressed in said modified stem cell; and   b) transferring said modified stem cell into an animal.   
     
     
         38 . The method of  claim 37 , wherein said animal is a human. 
     
     
         39 . The method of  claim 37 , wherein said contacting occurs ex vivo. 
     
     
         40 . The method of  claim 37 , wherein said stem cells are mobilized from said animal. 
     
     
         41 . The method of  claim 37 , wherein said mobilizing comprises administration of cytokines to said animal. 
     
     
         42 . The method of  claim 37 , wherein said transferring treats cancer in said subject. 
     
     
         43 . The method of  claim 37 , wherein said transferring prevents angiogenesis in said cancer. 
     
     
         44 . The method of  claim 37 , wherein said exogenous gene is expressed in platelet progenitors of said hematopoietic stem cell.