Non-invasive method for detecting target rna

C - Chemistry – Metallurgy – 12 – N

Patent

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C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2360997

The present invention provides a method for targeting a particular mRNA sequence <i>in vivo</i> by oral administration of a morpholino antisense compound having uncharged phosphorus-containing backbone linkages. Also disclosed is a non-invasive method of detecting and quantitating the <i>in vivo</i> presence of RNA containing one or more selected target sequences. The method includes administering to a subject a nuclease-resistant antisense oligomer which hybridizes by Watson-Crick base pairing to a region of the target RNA with a Tm substantially greater than 37 ~C. The oligomer is able to complex intracellularly with target RNA, and is release from intracellular sites as a nuclease-resistant heteroduplex, which can then be measured in a body fluid sample, e.g., urine.

La présente invention concerne un procédé pour cibler une séquence déterminée d'ARNm in vivo au moyen de l'administration orale d'un composé morpholino antisens possédant des liaisons de squelette et contenant du phosphore non chargé. L'invention concerne aussi un procédé non invasif de détection et de quantification in vivo de l'ARN présent contenant une ou plusieurs séquences cibles. Le procédé consiste à administrer à un sujet un oligomère antisens résistant à la nucléase s'hybridant par appariement de bases de Watson-Crick à une région de l'ARN cible, et ce à une Tm sensiblement supérieure à 37 ·C. L'oligomère est capable de former des complexes intracellulaires avec l'ARN cible et est libéré à partir de sites intracellulaires sous la forme d'un hétéroduplex résistant à la nucléase, qui peut ensuite être mesuré dans un échantillon d'un liquide corporel tel que l'urine.

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