Derivatized oligonucleotides having improved uptake and other properties

Claim 2

A compound comprising a plurality of linked nucleosides, wherein at least one of said nucleosides is functionalized at a 2'-O-position or a 2'-S-position thereof by attachment of a steroid molecule, an RNA cleaving complex, a porphyrin, or an aryl azide photo-crosslinking agent.

Claim 3

The compound of claim 1 wherein said functionalized nucleoside comprises a steroid molecule attached to the 2'-O-position or the 2'-S-position of said nucleoside, said steroid molecule being selected from the group consisting of cholic acid, deoxycholic acid, dehydrocholic acid, cortisone, digoxigenin, testosterone, cholesterol and digoxigenin.

Claim 4

The compound of claim 2 wherein said steroid molecule is cholesterol.

Claim 5

The compound of claim 1 wherein said functionalized nucleoside comprises an RNA cleaving complex attached to the 2'-O-position or the 2'-S-position of said nucleoside, said RNA cleaving complex being selected from the group consisting of a phenanthroline/metal complex and a bipyridine/metal complex.

Claim 6

The compound of claim 1 wherein said functionalized nucleoside comprises an aryl azide photo-crosslinking agent attached to the 2'-O-position or the 2'-S-position of said nucleoside.

Claim 7

The compound of claim 1 wherein said functionalized nucleoside comprises a porphyrin attached to the 2'-O-position or the 2'-S-position of said nucleoside.

Claim 8

The compound of claim 1 wherein folic acid is attached at the 2'-O-position or the 2'-S-position of said nucleoside.

Claim 9

The compound of claim 1 wherein cholic acid is attached at the 2'-O-position or the 2'-S-position of said nucleoside.

Claim 10

The compound of claim 8 wherein said attachment is through a linking moiety comprises an Ω-aminoalkoxy or Ω-aminoalkylamino moiety.

Claim 11

The compound of claim 9 wherein said linking moiety comprises an Ω-aminoalkoxy moiety.

Claim 12

The compound of claim 9 wherein said linking moiety comprises a 5-aminopentoxy group.

Claim 13

The compound of claim 1 wherein at least two of the linked nucleosides are linked by phosphorothioate linking groups.

Claim 14

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a 2' functionalized nucleoside having cholic acid linked to a 2'-O-position or a 2'-S-position of the nucleoside.

Claim 15

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a 2' functionalized nucleoside having cholic acid linked to a 2'-O-position or a 2'-S-position of the nucleoside.

Claim 16

The compound of claim 13 wherein a linking group links said cholic acid and the functionalized nucleoside.

Claim 17

The compound of claim 13 wherein at least one of the linked nucleosides is a 2'-deoxy'-2'-fluoro, 2'-methoxy, 2'-ethoxy, 2'-propoxy, 2'-aminoalkoxy or 2'-allyloxy nucleoside.

Claim 18

The compound of claim 13 wherein at least two of the linked nucleosides are linked by phosphorothioate linking groups.

Claim 19

The compound of claim 13 wherein said functionalized nucleoside is a 3' terminal nucleoside having cholesterol linked to the 3'-position of said 3' terminal nucleoside.

Claim 20

The compound of claim 13 wherein said functionalized nucleoside is a 5' terminal nucleoside having cholesterol linked to the 5'-position of said 5' terminal nucleoside.

Claim 21

The compound of claim 13 wherein said functionalized nucleoside is a heterocyclic base functionalized nucleoside having cholesterol linked to the heterocyclic base of said nucleoside.

Claim 22

The compound of claim 13 wherein said functionalized nucleoside is an inter-strand nucleoside having cholesterol linked to an inter-nucleotide linkage linking said inter-strand nucleoside to an adjacent nucleoside.

Claim 23

A compound comprising a plurality of linked nucleosides, wherein: at least one of the nucleosides is a 2'-deoxy'-2'-fluoro, 2'-O-C 1 -C 20 -alkyl, 2'-O-C 2 -C 20 -alkenyl, 2'-O-C 2 -C 20 -alkynyl, 2'-S-C 1 -C 20 -alkyl, 2'-S-C 2 -C 20 -alkenyl, or 2'-S-C 2 -C 20 -alkynyl nucleoside; and at least one of the nucleosides is a functionalized nucleoside selected from the group consisting of: a 2'-O-functionalized or a 2'-S-functionalized nucleoside having a steroid molecule, an RNA cleaving complex, a porphyrin, or an aryl azide photo-crosslinking agent linked to the 2'-position of the nucleoside; a heterocyclic base functionalized nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the heterocyclic base of the nucleoside; a 5' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/inter-calator, or an aryl azide photo-crosslinking agent linked to a 5'-O-position or a 5'-S-position of the nucleoside; a 3' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 3'-position of the nucleoside; and an inter-strand nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photo-nuclease/intercalator, or an aryl azide photo-crosslinking agent linked to an inter-stand linkage linking said inter-strand nucleoside to an adjacent nucleoside.

Claim 24

A compound comprising a plurality of linked nucleosides, wherein: at least one of the nucleosides is a 2'-deoxy'-2'-fluoro, 2'-O-C 1 -C 20 -alkyl, 2'-O-C 2 -C 20 -alkenyl, 2'-O-C 2 -C 20 -alkynyl, 2'-S-C 1 -C 20 -alkyl, 2'-S-C 2 -C 20 -alkenyl, or 2'-S-C 2 -C 20 -alkynyl nucleoside; and at least one of the nucleosides is a functionalized nucleoside selected from the group consisting of: a 2'-O-functionalized or a 2'-S-functionalized nucleoside having a steroid molecule, an RNA cleaving complex, a porphyrin, or an aryl azide photo-crosslinking agent linked to the 2'-position of the nucleoside; a heterocyclic base functionalized nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the heterocyclic base of the nucleoside; a 5' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/inter-calator, or an aryl azide photo-crosslinking agent linked to a 5'-O-position or a 5'-S-position of the nucleoside; a 3' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 3'-position of the nucleoside; and an inter-strand nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photo-nuclease/intercalator, or an aryl azide photo-crosslinking agent linked to an inter-stand linkage linking said inter-strand nucleoside to an adjacent nucleoside.

Claim 25

The compound of claim 21 wherein: said functionalized nucleoside is a nucleoside having a steroid molecule, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 2'-position of said nucleoside; and the remainder of said linked nucleosides are 2'-deoxy-2'-fluoro, 2'-methoxy, 2'-ethoxy, 2'-propoxy, 2'-aminoalkoxy or 2'-allyloxy nucleosides.

Claim 26

A compound comprising a plurality of linked nucleosides, wherein: at least one of the nucleosides is a 2'-deoxy'-2'-fluoro, 2'-O-C 1 -C 20 -alkyl, 2'-O-C 2 -C 20 -alkenyl, 2'-O-C 2 -C 20 -alkynyl, 2'-S-C 1 -C 20 -alkyl, 2'-S-C 2 -C 20 -alkenyl, 2'-S-C 2 -C 20 -alkynyl, 2'-NH-C 1 -C 20 -alkyl, 2'-NH-C 2 -C 20 -alkenyl, 2'-NH-C 2 -C 20 -alkynyl nucleoside; and at least one of the nucleosides is a 3' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 3'-position of the nucleoside.

Claim 27

A compound comprising a plurality of linked nucleosides, wherein: at least one of the nucleosides is a 2'-deoxy'-2'-fluoro, 2'-O-C 1 -C 20 -alkyl, 2'-O-C 2 -C 20 -alkenyl, 2'-O-C 2 -C 20 -alkynyl, 2'-S-C 1 -C 20 -alkyl, 2'-S-C 2 -C 20 -alkenyl, 2'-S-C 2 -C 20 -alkynyl, 2'-NH-C 1 -C 20 -alkyl, 2'-NH-C 2 -C 20 -alkenyl, 2'-NH-C 2 -C 20 -alkynyl nucleoside; and at least one of the nucleosides is a 3' terminal nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 3'-position of the nucleoside.

Claim 28

The compound of claim 21 wherein said functionalized nucleoside is a 5' nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the 5'-O-position or the 5'-S-position of the nucleoside.

Claim 29

The compound of claim 21 wherein said functionalized nucleoside is a heterocyclic base functionalized nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photo-nuclease/intercalator, or an aryl azide photo-crosslinking agent linked to the heterocyclic base of the nucleoside.

Claim 30

The compound of claim 21 wherein said functionalized nucleoside is an inter-strand nucleoside having a steroid molecule, a reporter molecule, an enzyme, a peptide, a protein, a vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent linked to an inter-strand linkage linking said nucleoside to an adjacent nucleoside.

Claim 31

The compound of claim 21 wherein at least two of the linked nucleosides are linked by phosphorothioate linking groups.

Claim 34

The method of claim 28 further including selecting said steroid molecule from the group consisting of cholic acid, deoxycholic acid, dehydrocholic acid, cortisone, digoxigenin, testosterone, cholesterol and digoxigenin.

Claim 35

The method of claim 28 further including selecting cholic acid as said steroid molecule.

Claim 36

The method of claim 28 further including selecting an Ω-amino alkylamino moiety as said linking molecule.

Claim 37

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a 2'-O-functionalized or 2'-S-functionalized nucleoside having folic acid linked to the 2' position of the nucleoside.

Claim 38

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a 2'-O-functionalized or 2'-S-functionalized nucleoside having folic acid linked to the 2' position of the nucleoside.

Claim 39

A compound of claim 32 wherein said functionalized nucleoside is a 2' functionalized nucleoside having folic acid linked to the 2' position of the nucleoside.

Claim 40

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a functionalized nucleoside selected from the group consisting of: a 5' terminal nucleoside having pyrene linked to the 5'-position of the nucleoside; a 3' terminal nucleoside having pyrene linked to the 3'-position of the nucleoside; and an inter-strand nucleoside having pyrene linked to an inter-nucleotide linkage linking said inter-strand nucleoside to an adjacent nucleoside.

Claim 41

A compound comprising a plurality of linked nucleosides, wherein at least one of the nucleosides is a functionalized nucleoside selected from the group consisting of: a 5' terminal nucleoside having pyrene linked to the 5'-position of the nucleoside; a 3' terminal nucleoside having pyrene linked to the 3'-position of the nucleoside; and an inter-strand nucleoside having pyrene linked to an inter-nucleotide linkage linking said inter-strand nucleoside to an adjacent nucleoside.