Lna modified phosphorothiolated oligonucleotides

C - Chemistry – Metallurgy – 07 – H

Patent

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Details

C07H 19/06 (2006.01) A61K 31/712 (2006.01) A61K 31/7125 (2006.01) A61K 31/713 (2006.01) C07H 19/16 (2006.01)

Patent

CA 2638837

The current invention provides oligonucleotides which comprise a dinucleotide consisting of a 5' locked nucleic acid (LNA), a phosphorothioate intemucloside linkage bond to a 3' RNA or RNA analogue. The dinucleotide reduces the strength of hybridization of the oligonucleotide to a complementary nucleic acid target. The modification can be used to modulate hybridisation properties in both single stranded oligonucleotides and in double stranded siRNA complexes, particularly in oligonucleotides where the use of LNA results in excessively strong hybridisation properties.

La présente invention concerne des oligonucléotides comportant un dinucléotide constitué d'un acide nucléique verrouillé 5', d'une liaison internucléoside phosphoré thiolé à un analogue ARN 3' ou d'ARN. Le dinucléotide réduit la force d'hybridation de l'oligonucléotide à une cible d'acide nucléique complémentaire. La modification peut être utilisée pour moduler des propriétés d'hybridation tant dans des oligonucléotides simple brin que dans des complexes d'ARNsi double brin, notamment dans des oligonucléotides où l'utilisation d'acides nucléiques verrouillés entraîne des propriétés d'hybridation excessivement fortes.

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