Method for opening tight junctions

Abstract

The use of antagonists to JAM-1 Claudin-4 and occludin to open tight junctions. The antagonists include, by way of example antibodies and antibody fragments that bind to the proteins and small interfering nucleic acids that downregulate the mRNA encoding the proteins.

1 . A formulation for administering a drug intranasally comprised of a drug, an antagonist that binds to an extracellular domain of a JAM-1 protein or an antagonist that binds to an extracellular domain of a claudin-4 protein or an antagonist that binds to an extracellular domain of a occludin protein.  
     
     
         2 . The formulation of  claim 1  wherein the formulation contains an antagonist of the JAM-1 protein and an antagonist to the claudin-4 protein.  
     
     
         3 . The formulation of  claim 1  wherein the formulation contains an antagonist of the JAM-1 protein and an antagonist to the occludin protein.  
     
     
         4 . The formulation of  claim 1  wherein the formulation contains an antagonist of the occludin protein and an antagonist to the claudin-4 protein.  
     
     
         5 . The formulation of  claim 1  wherein the formulation contains an antagonist of the JAM-1 protein, and antagonist to the occludin protein and an antagonist to the claudin-4 protein.  
     
     
         6 . The formulation  claim 1  wherein the antagonists are antibodies, fragments of antibodies or single-chain antibodies.  
     
     
         7 . A method for opening tight junctions in a tissue comprising bringing the tissue into with an antagonist that binds to an extracellular domain of a JAM-1 protein or an antagonist that binds to an extracellular domain of a claudin-4 protein or an antagonist that binds to an extracellular domain of a occludin protein.  
     
     
         8 . The method of  claim 7  further comprising bringing an antagonist of the JAM-1 protein and an antagonist to the claudin-4 protein into contact with the tissue so as to open the tight junction.  
     
     
         9 . The method of  claim 7  further comprising bringing an antagonist of the JAM-1 protein and an antagonist to the occludin protein into contact with the tissue so as to open the tight junction.  
     
     
         10 . The method of  claim 7  further comprising bringing an antagonist of the occludin and an antagonist to the claudin-4 protein into contact with the tissue so as to open the tight junction.  
     
     
         11 . The method of  claim 7  further comprising bringing an antagonist of a the JAM-1 protein and, an antagonist to the occludin protein an antagonist to the claudin-4 protein into contact with the tissue so as to open the tight junction.  
     
     
         12 . The method of  claim 7  wherein the antagonists are antibodies, fragments of antibodies or single-chain antibodies.  
     
     
         13 . The method of  claim 7  wherein the tissue is nasal mucosa.  
     
     
         14 . A formulation for administering a drug intranasally comprised of a drug, a small interfering nucleic acid (siNA) that down-regulates expression of a JAM-1 protein or a small interfering nucleic acid that down-regulates expression of a claudin-4 protein or a small interfering nucleic acid that down-regulates expression of a occludin protein.  
     
     
         15 . The formulation of  claim 14  wherein the formulation contains an siNA that can down-regulate the expression of the JAM-1 protein and an siNA that can down-regulate the expression of the claudin-4 protein.  
     
     
         16 . The formulation of  claim 14  wherein the formulation contains an siNA that can down-regulate the expression the JAM-1 protein and an siNA that can down-regulate the expression of the occludin protein.  
     
     
         17 . The formulation of  claim 14  wherein the formulation contains an siNA that can down-regulate the expression of the occludin protein and an siNA that can down-regulate the expression of the claudin-4 protein.  
     
     
         18 . The formulation of  claim 14  wherein the formulation contains an siNA that can down-regulate the expression the JAM-1 protein, an siNA that can down-regulate the expression of the claudin-4 protein and an siNA that can down-regulate the expression of the occludin protein.  
     
     
         19 . A method for opening tight junctions in a tissue comprising bringing the tissue into with a small interfering nucleic acid (siNA) that down-regulates expression of a JAM-1 protein or a small interfering nucleic acid that down-regulates expression of a claudin-4 protein or a small interfering nucleic acid that down-regulates expression of a occludin protein.  
     
     
         20 . The method of  claim 19  further comprising bringing an siNA that can down-regulate the expression of the JAM-1 protein and an siNA that can down-regulate the expression of the claudin-4 protein into contact with the tissue.  
     
     
         21 . The method of  claim 19  further comprising bringing an siNA that can down-regulate the expression the JAM-1 protein and an siNA that can down-regulate the expression of the occludin protein into contact with the tissue.  
     
     
         22 . The method of  claim 19  further comprising bringing an siNA that can down-regulate the expression of the occludin protein and an siNA that can down-regulate the expression of the claudin-4 protein into contact with the tissue.  
     
     
         23 . The method of  claim 19  further comprising bringing an siNA that can down-regulate the expression of the JAM-1 protein, an siNA that can down-regulate the expression of the claudin-4 protein and an siNA that can down-regulate the expression of the occludin protein into contact with the tissue so as to open the tight junction.  
     
     
         24 . The method of  claim 19  wherein the tissue is nasal mucosa.