Modified sirna molecules and uses thereof

Details Modified sirna molecules and uses thereof Modified sirna molecules and uses thereof

C - Chemistry, Metallurgy

07

H

C07H 21/02 (2006.01) A61K 9/127 (2006.01) A61K 31/713 (2006.01) A61K 47/44 (2006.01) C12Q 1/68 (2006.01)

Patent

CA 2628300

The present invention provides a chemically modified siRNA molecules and methods of using such siRNA molecules to silence target gene expression. Advantageously, the modified siRNA of the present invention is less immunostimulatory than its corresponding unmodified siRNA sequence and retains RNAi activity against the target sequence. The present invention also provides nucleic acid-lipid particles comprising a modified siRNA, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing gene expression by administering a modified siRNA to a mammalian subject. Methods for identifying and/or modifying an siRNA having immunostimulatory properties are also provided.

L'invention concerne des molécules d'ARNsi chimiquement modifiées et des procédés d'utilisation de celles-ci permettant de rendre silencieuse l'expression de gènes cibles. De manière avantageuse, l'ARNsi modifié de l'invention est moins immunostimulateur que sa séquence d'ARNsi non modifiée correspondante et retient l'activité de l'ARNi contre la séquence cible. L'invention concerne également des particules acides nucléiques-lipides comprenant un ARNsi modifié, un lipide cationique, un lipide non cationique, et éventuellement un lipide conjugué inhibant l'agrégation de particules. L'invention concerne également des procédés permettant de rendre silencieuse l'expression génique par administration d'un ARNsi modifié à un sujet mammifère. L'invention concerne en outre des procédés permettant d'identifier et/ou de modifier un ARNsi présentant des propriétés immunostimulatrices.

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