Cyclic di-nucleotide induction of type i interferon

Abstract

Methods and compositions are provided for increasing the production of a type I interferon (IFN) in a cell. Aspects of the methods include increasing the level of a 2′-5′ phosphodiester linkage comprising cyclic-di-nucleotide in a cell in a manner sufficient to increase production of the type I interferon (IFN) by the cell. Also provided are compositions and kits for practicing the embodiments of the methods.

1 . A method for increasing the production of a type I interferon (IFN) in a cell, the method comprising:
 increasing the level of a 2′-5′ phosphodiester linkage comprising cyclic-di-nucleotide in the cell in a manner sufficient to increase production of the type I interferon (IFN) by the cell.   
     
     
         2 . The method according to  claim 1 , wherein the method comprises contacting the cell with the cyclic-di-nucleotide. 
     
     
         3 . The method according to  claim 1 , wherein the cyclic-di-nucleotide comprises a two 2′-5′ phosphodiester linkage. 
     
     
         4 . The method according to  claim 3 , wherein the cyclic-di-nucleotide comprises a 2′5′ phosphodiester linkage and a 3′-5′ phosphodiester linkage. 
     
     
         5 . The method according to  claim 1 , wherein the cyclic-di-nucleotide comprises a guanosine nucleoside. 
     
     
         6 . The method according to  claim 5 , wherein the cyclic-di-nucleotide comprises two guanosine nucleosides. 
     
     
         7 . The method according to  claim 1 , wherein the cyclic-di-nucleotide comprises an adenosine nucleoside. 
     
     
         8 . The method according to  claim 7 , wherein the cyclic-di-nucleotide comprises two adenosine nucleosides. 
     
     
         9 . The method according to  claim 1 , wherein the cyclic-di-nucleotide comprises an adenosine nucleoside and a guanosine nucleoside. 
     
     
         10 . The method according to  claim 1 , wherein the cyclic-di-nucleotide is described by the formula: 
       
         
           
           
               
               
           
         
         wherein X and Y are each: 
       
       
         
           
           
               
               
           
         
       
     
     
         11 . The method according to  claim 10 , wherein the cyclic-di-nucleotide is described by the formula: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method according to  claim 1 , wherein the cyclic-di-nucleotide is described by the formula: 
       
         
           
           
               
               
           
         
         wherein X and Y are each: 
       
       
         
           
           
               
               
           
         
       
     
     
         13 . The method according to  claim 1 , wherein the level of the cyclic-di-nucleotide is increased by increasing the activity of a cGAMP synthase (cGAS) in the cell. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . The method according to  claim 1 , wherein the IFN is interferon alpha. 
     
     
         17 . The method according to  claim 1 , wherein the IFN is interferon beta. 
     
     
         18 . The method according to  claim 1 , wherein the cell is a mammalian cell. 
     
     
         19 . The method according to  claim 18 , wherein the mammalian cell is a human cell. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . A method for increasing the production of a type I interferon (IFN) in a subject, the method comprising:
 administering to the subject an amount of a 2′-5′ phosphodiester linkage comprising cyclic-di-nucleotide active agent effective to increase the production of the type I interferon in the subject.   
     
     
         23 - 42 . (canceled) 
     
     
         43 . A cyclic-di-nucleotide comprising a 2′-5′ phosphodiester linkage. 
     
     
         44 - 64 . (canceled) 
     
     
         65 . A method for increasing a stimulator of interferon genes (STING) mediated response in a subject, the method comprising:
 administering to the subject an amount of a STING active agent effective to increase a STING   
     
     
         66 - 86 . (canceled)