Car peptide for homing, diagnosis & targeted therapy for pulmonary and fibrotic disorders

Abstract

Disclosed are compositions and methods useful for delivering targeted therapies for pulmonary diseases, fibrotic disorders and cancer. The compositions and methods are based on peptide sequences that selectively bind to and home to diseased tissue and enable targeted therapies to effect a beneficial therapeutic result. The disclosed targeting is useful for delivering therapeutic and detectable agents to diseased tissue in an animal.

What is claimed is: 
     
         1 . A method of preventing or treating a disease comprising the steps of:
 (a) providing a targeting peptide comprising at least one amino acid sequence having substantial identity to a sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2; (b) providing at least one bioactive agent which conveys a measureable therapeutic benefit to the disease;   (c) co-administering a composition comprising (a) and (b) to an animal in need thereof; and   (d) measuring the therapeutic benefit to the animal.   
     
     
         2 . The method of  claim 1 , wherein the disease is pulmonary or fibrotic. 
     
     
         3 . The method of  claim 1 , wherein the disease is cancer. 
     
     
         4 . The method of  claim 1 , wherein the disease is an autoimmune disease. 
     
     
         5 . The method of  claim 1 , wherein the disease is heart failure or heart disease. 
     
     
         6 . The method of  claim 1 , wherein the disease is systemic inflammatory response or multiple organ failure. 
     
     
         7 . The method of  claim 1 , wherein the disease is bacterial or viral. 
     
     
         8 . The method of  claim 1 , wherein the targeting peptide comprises the amino acid sequence of SEQ ID NO:1. 
     
     
         9 . The method of  claim 6 , wherein the targeting peptide comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         10 . The method of  claim 1 , wherein the targeting peptide is isolated from an animal, bacteria, virus or is synthesized. 
     
     
         11 . The method of  claim 1 , wherein the targeting peptide and the at least one bioactive agent are bound. 
     
     
         12 . The method of  claim 1 , wherein the at least one bioactive agent is specific for the disease to be treated. 
     
     
         13 . A method of detecting an enhanced targeting effect of cell penetrating peptides in an animal comprising the steps of:
 (a) analyzing a sample from the animal for an altered level of at least one gene expression when compared to a control, wherein the at least one gene expressed encodes for a proteoglycan enzyme;   (b) correlating the altered level of at least one gene expression in the sample with the enhanced targeting effect of cell penetrating peptides; and   (c) treating the animal with a therapeutic composition comprising at least one cell penetrating peptide and at least one bioactive agent.   
     
     
         14 . The method of  claim 13 , wherein the at least one gene expressed encodes for an enzyme involved in heparan sulfate biosynthesis. 
     
     
         15 . The method of  claim 13 , wherein the altered level of at least one gene expression is an elevated level of the at least one gene expression. 
     
     
         16 . The method of  claim 11 , wherein the at least one gene having the altered level of expression is selected from the group consisting of heparan sulfate 2-O-sulfotransferase 1, exostosin 1, glycosyltransferase 8 domain containing 2, heparan sulfate N-deacetylase/N-sulfotransferase and O-linked N-acetylglucosamine transferase. 
     
     
         17 . The method of  claim 13 , wherein the enhanced targeting effect is targeted to heparan sulfate. 
     
     
         18 . The method of  claim 13 , wherein the therapeutic binds to heparan sulfate. 
     
     
         19 . The method of  claim 13 , wherein the at least one cell penetrating peptide is selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2. 
     
     
         20 . A method of treatment, comprising:
 (a) providing a targeting peptide comprising at least one amino acid sequence having substantial identity to a sequence selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2;   (b) providing at least one bioactive agent which conveys a measureable therapeutic benefit to the disease;   (c) co-administering a composition comprising (a) and (b) to an animal in need thereof, wherein the disease is associated with at least one alteration in an enzyme found to modulate heparan sulfate, which results in a modified heparan sulfate, and the composition comprising (a) and (b) is targeted to at least one heparan sulfate receptor.