Crosslinking oligonucleotides

C - Chemistry – Metallurgy – 07 – H

Patent

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Details

C07H 21/00 (2006.01) A61K 31/70 (2006.01) A61K 51/06 (2006.01) C12N 15/10 (2006.01) C12N 15/11 (2006.01) C12Q 1/68 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2223584

Oligonucleotides (ODNs) include a sequence that is complementary to a target sequence in single stranded RNA, or single or double stranded DNA, and an alkylating function which after hybridization alkylates the target sequence. ODNs adapted for alkylating single stranded RNA, such as messenger RNA, are complementary to the target sequence in the Watson Crick sense. ODNs adapted for alkylating double stranded DNA have at least two alkylating functions and are complementary to the target sequence in the Hoogsteen or reverse Hoogsteen sense. With these ODNs both strands of the target sequence are alkylated. A third class of ODNs have at least approximately 26 nucleotide units in a continuous sequence which are complementary to the target sequence of double stranded DNA, and the alkylating function is covalently attached to a nucleotide unit in the continuous sequence. Alkylation or cross-linking with this class of ODNs occurs in the presence of a recombinase enzyme.

Cette invention concerne des oligonucléotides (ODN) qui comportent une séquence complémentaire à une séquence cible dans de l'ARN monocaténaire, ou dans de l'ADN monocaténaire ou bicaténaire, ainsi qu'une fonction d'alcoylation qui, après hybridation, va alcoyler la séquence cible. Les ODN conçus pour alcoyler de l'ARN monocaténaire, tel que l'ARN messager, sont complémentaires à la séquence cible selon le processus de Watson Crick. Les ODN conçus pour alcoyler de l'ADN bicaténaire possèdent au moins deux fonctions d'alcoylation, et sont complémentaires à la séquence cible selon le principe de Hoogsteen, ou selon le principe inverse. Ces ODN permettent d'alcoyler les deux brims de la séquence cible. Les ODN d'une troisième classe comportent au moins environ 26 unités nucléotides dans une séquence continue, lesquelles unités sont complémentaires à la séquence cible d'ADN bicaténaire, la fonction d'alcoylation étant attachée par covalence à une unité nucléotidique de la séquence continue. L'alcoylation ou la réticulation avec cette classe d'ODN se fait en présence d'une recombinase.

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