MEDIATED CELLULAR DELIVERY OF LNA OLIGONUCLEOTIDES

• US 20100035968A1
• Filed: 01/18/2008
• Published: 02/11/2010
• Est. Priority Date: 01/19/2007
• Status: Active Grant

• Current Assignee: Qiagen GmbH (Qiagen NV)
• Original Assignee: Exiqon A/S (Qiagen NV)
• Inventors: Bryld, Torsten, Moeller, Soeren, Rasmussen, Soeren Vestergaard
• Granted Patent: US 8,048,998 B2
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

The present invention relates to novel modified oligomeric compounds and to methods of making and using such compounds. The invention further relates to methods of enhancing the cellular uptake of oligomeric compounds comprising conjugating a metal chelator to those.

Claims

1. (canceled)

2. (canceled)

3. A oligomeric compound of formula I:

OLIGO-L-CHEL  

 

(I)

wherein “

OLIGO”

designates an oligonucleotide composition containing at least one LNA monomer, “

CHEL”

designates a metal chelator and “

L”

is a linking moiety.

4. A compound of claim 3 wherein “

L”

is 6-(4-Monomethoxytritylamino)hexyl-(2-cyanoethyl)-(N,N-diisopropyl)-phosphoramidite.

5. A compound of claim 3 wherein the metal chelator is able to remove free metallic ions from solution by forming complexes.

6. A compound of claim 3 wherein the metal chelator is 2,2′

;

6′

,2″

-terpyridine, neocuproine or dipyridine.

7. A compound of claim 3 wherein the at least one LNA monomer are selected from oxy-LNA or amino-LNA.

8. A compound of claim 3 comprising one or more labels.

12. A method of treating a disease comprising administering a compound of claim 3 to an animal.

13. A compound of claim 3 with an antisense, silencing or knock-down efficacy.

9. A method of synthesising a compound of formula I

OLIGO-L-CHEL  

 

(I)

wherein “

OLIGO”

designates an oligonucleotide composition containing at least one LNA monomer, “

CHEL”

designates a metal chelator and “

L”

is a linking moiety, comprising the following steps;

a) coupling a linker moiety with a suitable solid phase protecting group to the 5′

-end of an oligonucleotide composition by a conventionally used process,

b) cleaving off said protecting group using a suitable reagent,

c) conjugating to said linker moiety a metal chelator, and

d) deprotecting said oligonucleotide composition.

10. A method of synthesising a compound of formula I

OLIGO-L-CHEL  

 

(I)

wherein “

OLIGO”

designates an oligonucleotide composition containing at least one LNA monomer, “

CHEL”

designates a metal chelator and “

L”

is a linking moiety, comprising the following steps;

a) attaching a linker moiety to the solid phase by conventionally used processes, thereby attaching the linker to the 3′

-end of an oligonucleotide,

b) synthesising an oligonucleotide composition using conventionally used processes,

c) deprotecting said oligonucleotide composition, and

d) conjugating to said linker moiety a metal chelator.

11. A kit comprising a compound of formula I

OLIGO-L-CHEL  

 

(I)

wherein “

OLIGO”

designates an oligonucleotide composition, “

CHEL”

designates a metal chelator and “

L”

is a linking moiety for use in diagnostics.