A compound having Formula I: wherein, R 1 is H, OH, C 1-6 alkyl, C 1-6 alkyl substituted with one or more hydroxyl groups, C 1-6 alkyl substituted with one or more halo groups, C 1-6 alkenyl, C 1-6 alkenyl substituted with one or more hydroxyl groups, C 1-6 alkenyl substituted with one or more halo groups, C 1-6 alkynyl, C 1-6 alkynyl substituted with one or more hydroxyl groups, C 1-6 alkynyl substituted with one or more halo groups, C 1-6 alkoxyl, C 1-6 alkoxyl substituted with one or more hydroxyl groups, C 1-6 alkoxyl substituted with one or more halo groups, aryl, heteroaryl, heterocyclyl, - NHC 1-6 alkyl, arylC 1-6 alkyl, heteroarylC 1-6 alkyl, heterocyclylC 1-6 alkyl, guanidinyl, C 1-6 alkylC O-, arylC O-, heterocyclylC O-, O-propargyl, S-propargyl, O-allyl, S-allyl, or X-L-Y; wherein X is O, S, NH, C, S, C 1-6 alkyl, C 1-6 alkyl substituted with one or more hydroxyl groups, C 1-6 alkyl substituted with one or more halo groups, C 1-6 alkenyl, C 1-6 alkenyl substituted with one or more hydroxyl groups, C 1-6 alkenyl substituted with one or more halo groups, C 1-6 alkynyl, C 1-6 alkynyl substituted with one or more hydroxyl groups, C 1-6 alkynyl substituted with one or more halo groups, C 1-6 alkoxyl, C 1-6 alkoxyl substituted with one or more hydroxyl groups, C 1-6 alkoxyl substituted with one or more halo groups, aryl, heteroaryl, heterocyclyl, -NHC 1-6 alkyl, arylC 1-6 alkyl, heteroarylC 1-6 alkyl, heterocyclylC 1-6 alkyl, guanidinyl, C 1-6 alkylC O-, arylC O-, heterocyclylC O-, O-propargyl, S-propargyl, O-allyl, S-allyl; L is a linker that is optionally present; and Y is a targeting agent, ligand and/or polymer that is optionally present; R 4 is S or O; each R 2, R 3, R 5, R 6, R 7 and R 8 is independently halo or R 1 as above; R 9 is O-phenyl, O-naphthyl, or O-benzyl any of which can be substituted with one or more halo groups; or an amine, substituted amine, NH-benzyl, NHR 12 or N(R 12) 2, wherein each R 12 is independently H, C 1-10 alkyl, or C 1-10 alkyl substituted with one or more halo groups; R 10 is S or O; and NUC is a nucleoside or nucleotide. R 1 is H, OH, C 1-6 alkyl, C 1-6 alkyl substituted with one or more hydroxyl groups, C 1-6 alkyl substituted with one or more halo groups, C 1-6 alkenyl, C 1-6 alkenyl substituted with one or more hydroxyl groups, C 1-6 alkenyl substituted with one or more halo groups, C 1-6 alkynyl, C 1-6 alkynyl substituted with one or more hydroxyl groups, C 1-6 alkynyl substituted with one or more halo groups, C 1-6 alkoxyl, C 1-6 alkoxyl substituted with one or more hydroxyl groups, C 1-6 alkoxyl substituted with one or more halo groups, aryl, heteroaryl, heterocyclyl, - NHC 1-6 alkyl, arylC 1-6 alkyl, heteroarylC 1-6 alkyl, heterocyclylC 1-6 alkyl, guanidinyl, C 1-6 alkylC O-, arylC O-, heterocyclylC O-, O-propargyl, S-propargyl, O-allyl, S-allyl, or X-L-Y; wherein X is O, S, NH, C, S, C 1-6 alkyl, C 1-6 alkyl substituted with one or more hydroxyl groups, C 1-6 alkyl substituted with one or more halo groups, C 1-6 alkenyl, C 1-6 alkenyl substituted with one or more hydroxyl groups, C 1-6 alkenyl substituted with one or more halo groups, C 1-6 alkynyl, C 1-6 alkynyl substituted with one or more hydroxyl groups, C 1-6 alkynyl substituted with one or more halo groups, C 1-6 alkoxyl, C 1-6 alkoxyl substituted with one or more hydroxyl groups, C 1-6 alkoxyl substituted with one or more halo groups, aryl, heteroaryl, heterocyclyl, -NHC 1-6 alkyl, arylC 1-6 alkyl, heteroarylC 1-6 alkyl, heterocyclylC 1-6 alkyl, guanidinyl, C 1-6 alkylC O-, arylC O-, heterocyclylC O-, O-propargyl, S-propargyl, O-allyl, S-allyl; L is a linker that is optionally present; and Y is a targeting agent, ligand and/or polymer that is optionally present; R 4 is S or O; each R 2, R 3, R 5, R 6, R 7 and R 8 is independently halo or R 1 as above; R 9 is O-phenyl, O-naphthyl, or O-benzyl any of which can be substituted with one or more halo groups; or an amine, substituted amine, NH-benzyl, NHR 12 or N(R 12) 2, wherein each R 12 is independently H, C 1-10 alkyl, or C 1-10 alkyl substituted with one or more halo groups; R 10 is S or O; and NUC is a nucleoside or nucleotide.