Polymeric carrier

Abstract

Provided herein are polymeric carriers suitable for the delivery of polynucleotides (e.g., oligonucleotides) and/or other therapeutic agents into a living cell.

What is claimed is: 
     
         1 . A polymeric carrier comprising:
 (a) a plurality of polymers that are block copolymers assembled into a polymeric carrier, the polymeric carrier comprising a core and a shell, the block copolymers having the chemical Formula I:   
       
         
           
           
               
               
           
         
         wherein
 each of A 0 , A 1 , A 2 , A 3  and A 4  is —C—C—; 
 each of Y 0  and Y 1  is —C(O)O(2C-10C)alkyl-; 
 Y 2  is —C(O)OCH 2 CH 2 —; 
 Y 3  is a covalent bond; 
 Y 4  1 S—C(O)O(CH 2 ) 3 CH 3 ; 
 wherein tetravalent carbon atoms of A 0 -A 4  that are not fully substituted with R 1 -R 5  and Y 0 -Y 4  are completed with an appropriate number of hydrogen atoms; 
 each of R 1 , R 2 , R 3 , and R 5  is (1C-5C)alkyl; 
 R 4  is —CH 2 CH 2 CH 3 ; 
 Q 0  is a residue selected from the group consisting of polyoxylated alkyl, polyethylene glycol, and polypropylene glycol; 
 Q 1  is a residue selected from the group consisting of amino, alkylamino, ammonium, alkylammonium, and guanidine; 
 Q 2  is a dimethylamino residue; 
 Q 3  is a carboxyl residue;
 m is 0 to less than 1.0; 
 n is greater than 0 to 1.0, wherein m+n=1; 
 p is 0.1 to 0.9; 
 q is 0.1 to 0.9; 
 r is 0 to 0.8 wherein p+q+r=1; 
 v is 1 to 25 kDa; and 
 w is 1 to 50 kDa; and 
 
 
         (b) at least one polynucleotide, 
         wherein the polynucleotide is not in the core of the polymeric carrier. 
       
     
     
         2 . The polymeric carrier of  claim 1 , wherein Q 0  is a polyethylene glycol residue. 
     
     
         3 . The polymeric carrier of  claim 1 , wherein Q 1  is an alkylamino residue. 
     
     
         4 . The polymeric carrier of  claim 3 , wherein Q 1  is a dimethylamino residue. 
     
     
         5 . The polymeric carrier of  claim 1 , wherein
 Y 0  is —C(O)OCH 2 CH 2 —; and   R 1  is —CH 3 .   
     
     
         6 . The polymeric carrier of  claim 1 , wherein
 Y 1  is —C(O)OCH 2 CH 2 —; and   R 2  is —CH 3 .   
     
     
         7 . The polymeric carrier of  claim 1 , wherein R 3  is —CH 3 . 
     
     
         8 . The polymeric carrier of  claim 1 , wherein R 5  is —CH 3 . 
     
     
         9 . The polymeric carrier of  claim 1 , wherein m is 0. 
     
     
         10 . The polymeric carrier of  claim 9 , wherein Q 1  is an alkylamino residue. 
     
     
         11 . The polymeric carrier of  claim 10 , wherein Q 1  is a dimethylamino residue. 
     
     
         12 . The polymeric carrier of  claim 1 , wherein the polynucleotide is an oligonucleotide. 
     
     
         13 . The polymeric carrier of  claim 12 , wherein the polynucleotide is an siRNA. 
     
     
         14 . The polymeric carrier of  claim 1 , further comprising a targeting moiety. 
     
     
         15 . The polymeric carrier of  claim 14 , wherein the targeting moiety is attached to the shell portion by a covalent bond to a polymer. 
     
     
         16 . The polymeric carrier of  claim 1 , wherein the plurality of polymers have spontaneously self-assembled into the polymeric carrier. 
     
     
         17 . The polymeric carrier of  claim 1 , wherein v is 5 to 25 kDa. 
     
     
         18 . The polymeric carrier of  claim 1 , wherein w is 5 to 50 kDa. 
     
     
         19 . A composition comprising the polymeric carrier of  claim 1 . 
     
     
         20 . A method for intracellular delivery of a polynucleotide to a cell, the method comprising contacting a cell with the polymeric carrier of  claim 1 .