Membrane lytic poly(amido amine) polymers for the delivery of oligonucleotides

1. A polymer comprising Formula Z:

wherein:

n is 2 to 250;

R 1 is independently selected from the group consisting of a primary amine, secondary amine, tertiary amine, and quaternary amine; and

R 2 is independently selected from the group consisting of a primary amine, secondary amine, tertiary amine, quaternary amine, a heterocyclic amine, and a lipophilic group;

or stereoisomer thereof.

2. A polymer according to claim 1 comprising Formula Z′:

wherein:

n is 2 to 250;

R is a capped end group selected from the group consisting of a primary amine and secondary amine;

R′ is hydrogen or methylene;

R 1 is independently selected from the group consisting of a primary amine, secondary amine, tertiary amine, and quaternary amine; and

R 2 is independently selected from the group consisting of a primary amine, secondary amine, tertiary amine, quaternary amine, a heterocyclic amine, and a lipophilic group;

or stereoisomer thereof.

3. A polymer according to claim 1 comprising Formula Z′, wherein:

n is 2 to 250;

R is C 4 H 10 N;

R′ is hydrogen;

R 1 is aminoethoxy; and

R 2 is independently selected from dodecyl, 2-(1H-imidazol-4-yl)ethyl and 2-(2-aminoethoxy)ethyl;

or stereoisomer thereof.

4. A polymer according to claim 1 which is selected from:

wherein the polymer is random or block and wherein n′, n″, and n′″ are independently 0 to 60, provided that the sum of n′, n″, and n′″ is at least 2; R is C 4 H 10 N; and R′ is hydrogen.

5. A polymer conjugate composition comprising a polymer according to claim 1 of Formula Z, a linker and an oligonucleotide.

6. A polymer conjugate composition of claim 5 further comprising a masking agent.

7. A polymer conjugate composion of claim 5 further comprising a targeting ligand.

8. A polymer conjugate composition of claim 5 further comprising a masking agent and a targeting ligand.

9. A polymer conjugate composition made by the

1) synthesis of an activated polymer comprising Formula Z:

wherein:

n is 2 to 250;

R 1 is independently selected from the group consisting of a primary amine, secondary amine, tertiary amine, and quaternary amine; and

R 2 is independently selected from a primary amine, secondary amine, tertiary amine, quaternary amine, a heterocyclic amine, and a lipophilic group;

or stereoisomer thereof;

2) synthesis of an activated oligonucleotide; and

3) conjugation of the activated polymer with the activated oligonucleotide;

optionally including the addition of a masking agent and/or a targeting ligand.