Ptd-smad7 therapeutics

Abstract

The present technology provides methods and compositions for the treatment of inflammatory and/or tissue damage conditions. In particular, the use of Smad7 compositions delivered locally or systemically to a site of inflammation and/or tissue damage is described. Other specific embodiments concern treatment or prevention of side effects caused by radiation and/or chemotherapy, including but not limited to oral and gastric mucositis. Also provided are codon-optimized nucleic acids encoding for Smad7 fusion proteins.

What is claimed is: 
     
         1 - 48 . (canceled) 
     
     
         49 . A protein molecule comprising a protein transduction domain and a human mothers against decapentaplegic-7 protein (Smad7) fragment comprising amino acids 259-426 of the human Smad7 protein, wherein the Smad7 fragment retains one or more biological activities of the functional full-length Smad7 protein, and with the proviso that the protein molecule lacks at least amino acids 1-203 of the human Smad7 protein. 
     
     
         50 . The protein molecule of  claim 49 , wherein the human mothers against decapentaplegic-7 protein (Smad7) fragment consists of amino acids 259-426 of the human Smad7 protein. 
     
     
         51 . The protein molecule of  claim 49 , wherein the protein transduction domain is Tat. 
     
     
         52 . The protein molecule of  claim 50 , wherein the protein transduction domain is Tat. 
     
     
         53 . A pharmaceutical composition comprising the protein molecule of  claim 49 , and one or more pharmaceutically acceptable excipients. 
     
     
         54 . A method for treating an inflammatory condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the protein molecule of  claim 49 . 
     
     
         55 . The method of  claim 54 , wherein the inflammatory condition is selected from the group consisting of radiation-induced damage, psoriasis, stomatitis, proctitis, ulcerative colitis, Crohn's disease, irritable bowel disease, and inflammatory bowel disease. 
     
     
         56 . A method for treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the protein of  claim 49 , wherein the administration of the protein results in an increase in one or more of cell proliferation or cell migration, or reducing one or more of apoptosis or DNA damage in the subject. 
     
     
         57 . A method for treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the protein of  claim 49 , wherein the disease or disorder is selected from the group consisting of promoting wound healing, treating inflammatory diseases, aberrant healing, auto-immune diseases and auto-immune disorders. 
     
     
         58 . The method of  claim 57 , wherein the promoting wound healing comprises promoting wound healing of chronic wounds, acute wounds or mucositis. 
     
     
         59 . The method of  claim 58 , wherein the chronic wounds are selected from the group consisting of diabetic ulcers, pressure ulcers, venous ulcers, and oral ulcers. 
     
     
         60 . The method of  claim 58 , wherein the acute wounds are selected from the group consisting of trauma-induced wounds, surgical wounds, and scarring. 
     
     
         61 . The method of  claim 58 , wherein the promoting healing in mucositis comprises promoting healing in radiation-induced mucositis and chemotherapy-induced mucositis. 
     
     
         62 . The method of  claim 58 , wherein the mucositis is selected from the group consisting of oral mucositis and gastrointestinal mucositis. 
     
     
         63 . The method of  claim 57 , wherein the aberrant healing comprises scarring and fibrosis. 
     
     
         64 . The method  claim 57 , wherein the autoimmune diseases and auto-immune disorders are selected from the group consisting of psoriasis, stomatitis, proctitis, ulcerative colitis, Crohn's disease, irritable bowel disease, and inflammatory bowel disease.