NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF

1 . A molecule of Formula:

A-B-(D)n

wherein,

A is a binding moiety;

B is a polynucleotide;

D is an endosomolytic moiety, wherein D is conjugated to the 3′ end or an internal position of B; and

n is an integer from 1 to 10.

2 . The molecule of claim 1 , wherein the binding moiety is an antibody or antigen binding fragment thereof.

3 . The molecule of claim 1 , wherein the polynucleotide comprises at least one 2′ modified nucleotide, at least one modified internucleotide linkage, or at least one inverted abasic moiety

4 . The molecule of claim 3 , wherein the at least one 2′ modified nucleotide comprises 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl, 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), or 2′-O—N-methylacetamido (2′-O-NMA) modified nucleotide.

5 . The molecule of claim 3 , wherein the at least one 2′ modified nucleotide comprises locked nucleic acid (LNA) or ethylene nucleic acid (ENA).

6 . The molecule of claim 3 , wherein the at least one modified internucleotide linkage comprises a phosphorothioate linkage or a phosphorodithioate linkage.

7 . The molecule of claim 3 , wherein the at least one inverted abasic moiety is at at least one terminus.

8 . The molecule of claim 1 , wherein the polynucleotide hybridizes to a target region selected from growth factors or mitogens, receptor tyrosine kinases, cytoplasmic tyrosine kinases, cytoplasmic serine/threonine kinases, and regulatory GTPases, and transcription factors.

9 . The molecule of claim 1 , wherein the polynucleotide comprises a single-stranded polynucleic acid molecule.

10 . The molecule of claim 1 , wherein the polynucleotide comprises a first polynucleotide and a second polynucleotide hybridized to the first polynucleotide to form a double-stranded polynucleic acid molecule.

11 . The molecule of claim 10 , wherein the second polynucleotide comprises at least one modification.

12 . The molecule of claim 10 , wherein the first polynucleotide and the second polynucleotide are RNA molecules.

13 . The molecule of claim 2 , wherein the antibody or antigen binding fragment thereof binds to a cell surface receptor selected from epidermal growth factor receptor (EGFR), interleukin-2 receptor (IL-2R), transferrin receptor, endothelin receptor type B (ETRB), interleukin-20 receptor subunit alpha (IL20Ra), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) receptor.

14 . The molecule of claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a humanized antibody or antigen-binding fragment thereof, chimeric antibody or antigen-binding fragment thereof, monoclonal antibody or antigen-binding fragment thereof, monovalent Fab′, divalent Fab2, single-chain variable fragment (scFv), diabody, minibody, nanobody, single-domain antibody (sdAb), or camelid antibody or antigen-binding fragment thereof.

15 . The molecule of claim 1 , wherein the endosomolytic moiety comprises an endosomolytic polypeptide, an endosomolytic polymer, an endosomolytic lipid, or an endosomolytic small molecule.

16 . The molecule of claim 15 , wherein the endosomolytic polypeptide comprises INF7 or melittin.

17 . The molecule of claim 1 , further comprising C, wherein C is a polymer.

18 . The molecule of claim 17 , wherein the polymer is polyethylene glycol.

19 . A molecule of Formula:

A-D-B

wherein,

A is a binding moiety;

B is a polynucleotide; and

D is an endosomolytic moiety, wherein D is conjugated to the 3′ end or an internal position of B.

20 . A pharmaceutical composition comprising:

the molecule of claim 1 ; and

a pharmaceutically acceptable excipient.