Multiblock copolymers

1. A composition comprising a block copolymer associated with a polynucleotide, the block copolymer consisting of a first, a second and a third compositionally distinct blocks,

wherein the first block is a hydrophilic polymer block consisting of repeat units derived from polymerization of a monomer of Formula IV

wherein

each R 1 and R 2 , is hydrogen,

R 3 is C 1 -C 3 alkyl,

n is an integer ranging from 2 to 20,

R 8 is (CR 1 R 2 ) m R 9 , wherein m is 0-10, and

R 9 is a targeting group,

wherein the second block is located between the first and third blocks and is associated with the polynucleotide, wherein the second block consists of a plurality of monomeric residues of amino(C 1 -C 6 )alkyl-methacrylate, N-(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl -methacrylate, N,N-di(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-methacrylate, or a combination thereof, or wherein the second block is a random copolymer consisting of two compositionally distinct repeat units, wherein one of said repeat units is a monomeric residue of 2-hydroxypropyl methacrylate, N-(2-propyl)methacrylamide, or N-propylmethacrylate, and the other of said repeat units has Formula 1

wherein

* designates the point of attachment of the repeat unit of Formula 1 to other repeat units;

each of X 1 and X 2 is hydrogen;

X 3 for Formula 1 within the second block is alkyl, and

X 4 is —C(O)OX 45 , wherein X 45 is a disulfide substituted alkyl moiety, and

wherein the third block is a hydrophobic polymer block consisting of repeat units having Formulae 1A, 1E, and 1C

wherein * designates the point of attachment of the repeat units of Formula 1A, 1E, and 1C to other repeat units, X 3 for Formula 1A is propyl, X 3 for each of Formulae 1E and 1C is methyl, X 47 is butyl, and X 48 is N,N-dimethylaminoethyl.

2. The composition of claim 1 wherein the ratio of the number of repeat units having Formula 1A to the number of repeat units corresponding to Formula 1E in the third block is between about 20:1 and 1:4, respectively.

3. The composition of claim 1 wherein the number of repeat units having Formula 1A in the third block is at least equal to the number of repeat units having Formula 1C in third block.

4. The composition of claim 1 wherein the polynucleotide is a deoxyribonucleotide, an siRNA, an antisense oligonucleotide, a dicer substrate, an miRNA, an aiRNA or an shRNA.

5. The composition of claim 4 wherein the polynucleotide is an siRNA.

6. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable excipient.

7. The composition of claim 1 wherein X 45 comprises the polynucleotide, and the polynucleotide is covalently bound to the composition through the disulfide moiety of X 45 .

8. The composition of claim 1 wherein X 45 is pyridyl disulfide substituted ethyl.

9. The composition of claim 1 wherein the targeting moiety group is galactose, N-acetyl galactosamine, or folate.

10. A composition comprising a polymeric micelle and a polynucleotide associated with the micelle, the micelle comprising a plurality of block copolymers consisting of

(i) a first block, wherein the first block is a hydrophilic polymer block consisting of repeat units derived from polymerization of a monomer of Formula IV

wherein

each R 1 and R 2 is hydrogen,

R 3 is C 1 -C 3 alkyl,

n is an integer ranging from 2 to 20,

R 8 is (CR 1 R 2 ) m R 9 , wherein m is 0-10, and

R 9 is a targeting group,

(ii) a second block between the first block and a third block, wherein the second block is associated with the polynucleotide, wherein the second block consists of a plurality of monomeric residues of amino(C 1 -C 6 )alkyl-methacrylate, N-(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-methacrylate, N,N-di(C 1 -C 6 )alkyl-amino(C 1 -C 6 )alkyl-methacrylate, or a combination thereof, or wherein the second block is a random copolymer consisting of two compositionally distinct repeat units, wherein one of said repeat units is a monomeric residue of 2-hydroxypropyl methacrylate, N-(2-propyl)methacrylamide, or N-propylmethacrylate, and the other of said repeat units has Formula 1

wherein

* designates the point of attachment of the repeat unit of Formula 1 to other repeat units;

each of X 1 and X 2 is hydrogen;

X 3 for Formula 1 within the second block is alkyl, and

X 4 is —C(O)OX 45 , wherein X 45 is a disulfide substituted alkyl moiety, and

(iii) a third block, wherein the third block is a polymer block consisting of repeat units having Formulae 1A, 1E, and 1C

wherein * designates the point of attachment of the repeat units of Formula 1A, 1E, and 1C to other repeat units, X 3 for Formula 1A is propyl, X 3 for each of Formulae 1E and 1C is methyl, X 47 is butyl, and X 48 is N,N-dimethylaminoethyl, and

wherein the micelle is stable in an aqueous medium at pH 7.4.

11. The composition of claim 10 wherein the polynucleotide is a deoxyribonucleotide, an siRNA, an antisense oligonucleotide, a dicer substrate, an miRNA, an aiRNA or an shRNA.

12. A method for intracellular delivery of a polynucleotide, comprising transfecting a cell with a composition of claim 1 .