NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF

1 . A polynucleotide conjugate molecule comprising a binding moiety and a polynucleotide, wherein the polynucleotide comprises (i) at least one 5′-vinylphosphonate modified non-natural nucleotide and (ii) at least one modified internucleotide linkage or at least one inverted abasic moiety; and

wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is:

wherein B is a heterocyclic base moiety; and

J is an internucleotide linking group linking to the adjacent nucleotide of the polynucleotide.

2 . The molecule of claim 1 , wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is located at the 5′-terminus of the polynucleotide.

3 . The molecule of claim 1 , wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is located at an internucleotide linkage of the polynucleotide.

4 . The molecule of claim 1 , wherein the at least one 5′-vinylphosphonate modified non-natural nucleotide is further modified at the 2′-position.

5 . The molecule of claim 5 , wherein the 2′-modification is selected from 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 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), 2′-O—N-methylacetamido (2′-O-NMA), 2′-O-ethyoxyethyl (2′-O-EOE), 2′-O-(2-N-Methylcarbamoylethyl), PEG1, or PEG2 modified nucleotide.

6 . The molecule of claim 1 , wherein the at least one modified internucleotide linkage comprises a phosphorothioate linkage, a phosphorodithioate linkage, a phosphorodiamidate linkage, a methylphosphonate linkage, or an amide linkage.

7 . The molecule of claim 1 , wherein the at least one inverted abasic moiety is at at least one terminus.

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

9 . 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.

10 . The molecule of claim 9 , wherein the second polynucleotide comprises at least one modification.

11 . The molecule of claim 9 , wherein the first polynucleotide and the second polynucleotide are RNA molecules.

12 . The molecule of claim 1 , wherein the binding moiety and the polynucleotide is coupled via a bond; a C 1 -C 6 alkyl group; or a homobifunctional linker or a heterobifunctional linker, optionally conjugated to a C 1 -C 6 alkyl group.

13 . The molecule of claim 1 , further comprising a polymer.

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

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

16 . The molecule of claim 1 , wherein the binding moiety comprises a peptide or a small molecule.

17 . The molecule of claim 16 , wherein the polymer is polyethylene glycol.

18 . The molecule of claim 16 , wherein the polymer has a molecular weight of about 1000 Da, 2000 Da, or 5000 Da.

19 . The molecule of claim 1 , further comprising an endosomolytic moiety.

20 . A compound suitable for the synthesis of an oligonucleotide, wherein the compound is selected from the group:

wherein B is a heterocyclic base moiety.