Vectors Conditionally Expressing Protein

Abstract

This invention relates to the field of therapeutics. Disclosed are methods of generating conditionally expressing erythropoietin under the control of an ecdysone receptor-based gene expression modulation system in the presence of activating ligand and uses for therapeutic purposes in animals. The methods of the invention cause an in vivo increase in the expression of erythropoietin and an increase in the hematocrit or volume percentage of red blood cells in blood after administration of the ligand.

1 - 39 . (canceled) 
     
     
         40 . A method for treating a disease in a mammal, comprising:
 (a) administering to the mammal a vector for conditionally expressing one or more proteins, the vector comprising a polynucleotide encoding a gene switch, wherein the polynucleotide comprises
 (1) at least one transcription factor sequence which is operably linked to a promoter, wherein the at least one transcription factor sequence encodes a ligand-dependent transcription factor, and 
 (2) a polynucleotide encoding one or more proteins operably linked to a promoter which is activated by the ligand-dependent transcription factor, and 
   (b) administering to the mammal a therapeutically effective amount of one or more activating ligands; thereby inducing expression of the one or more proteins and treating the disease,   wherein the one or more proteins is selected from the group consisting of a C1 esterase inhibitor, a kallikrein inhibitor, a bradykinin B2 receptor inhibitor, a prostaglandin synthase, a glucagon-like peptide-1 (GLP-1), a glucagon-like peptide-2 (GLP-2), adiponectin, leptin, and cystic fibrosis transmembrane conductance regulator (CFTR).   
     
     
         41 . The method of  claim 40 , wherein at least one of the proteins is a C1 esterase inhibitor and the disease is selected from the group consisting of angioedema, hereditary angioedema, sepsis, hypercoagulability, pulmonary dysfunction, hypoxemia, hemorrhagic pancreatitis, myocardial infarction, lung transplantation, trauma, thermal injury, or vascular leak. 
     
     
         42 . The method of  claim 40 , wherein at least one of the proteins is a kallikrein inhibitor and the disease is selected from the group consisting of angioedema, hereditary angioedema, atherothrombosis, coronary artery disease, Alzheimer's Disease, inflammatory bowel disease, Crohn's Disease, vascular leak, acute respiratory distress syndrome, bradykinin-mediated inflammation and a disease, condition or disorders of the contact system. 
     
     
         43 . The method of  claim 40 , wherein at least one of the proteins is a bradykinin B2 receptor inhibitor and the disease is selected from the group consisting of angioedema, hereditary angioedema, bradykinin-mediated inflammation, glomerulosclerosis, Alzheimer's Disease, cerebral edema, vascular leak, acute respiratory distress syndrome, pain, inflammation, trauma, burns, shock, allergy, and cardiovascular disease. 
     
     
         44 . The method of  claim 40 , wherein at least one of the proteins is a prostaglandin synthase and the disease is selected from the group consisting of pulmonary hypertension, pulmonary arterial hypertension (PAH), idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, secondary pulmonary arterial hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, persistent pulmonary hypertension of the newborn. 
     
     
         45 . The method of  claim 40 , wherein at least one of the proteins is a glucagon-like peptide-1 (GLP-1) and the disease is diabetes or other metabolic disease or disorder. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 40 , wherein at least one of the proteins is adiponectin and the disease is diabetes or other metabolic disease or disorder. 
     
     
         48 . (canceled) 
     
     
         49 . The method of  claim 40 , wherein at least one of the proteins is cystic fibrosis transmembrane conductance regulator (CFTR) and the disease is cystic fibrosis. 
     
     
         50 - 85 . (canceled) 
     
     
         86 . The method of  claim 40 , wherein at least one of the proteins is a human protein. 
     
     
         87 . The method of  claim 40 , wherein the vector is a viral vector. 
     
     
         88 . The method of  claim 87 , wherein the wherein the viral vector is selected from the group consisting of an adenovirus, an adeno-associated virus, a retrovirus, a pox virus, a baculovirus, a vaccinia virus, a herpes simplex virus, an Epstein-Barr virus, a geminivirus, a pseudorabies virus, a parvovirus, and a caulimovirus virus vector. 
     
     
         89 . The method of  claim 40 , wherein the gene switch is an ecdysone receptor (EcR)-based gene switch. 
     
     
         90 . The method of  claim 89 , wherein the polynucleotide encoding a gene switch comprises a first transcription factor sequence under the control of a first promoter and a second transcription factor sequence under the control of a second promoter, wherein a first transcription factor encoded by the first transcription factor sequence and a second transcription factor encoded by the second transcription factor sequence interact to form a complex which functions as a ligand-dependent transcription factor.