Selective killing of cells by activation of double-stranded...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 31/7088 (2006.01) A61P 9/10 (2006.01) A61P 17/06 (2006.01) A61P 35/00 (2006.01) C12N 5/10 (2006.01) C12N 9/12 (2006.01) C12N 15/63 (2006.01) C12N 15/867 (2006.01)

Patent

CA 2398678

Novel methods and compositions for selective killing of cells by activation of PKR are disclosed. In a preferred embodiment, a method is provided for causing cell death in a targeted population of cells that includes the steps of: selecting a nucleotide sequence at a single genetic locus in the targeted population that is absent from the equivalent locus in a population of non- targeted cells; obtaining one or more anti-sense RNA having sequence homology with the locus in the targeted population; permitting the anti-sense RNA to hybridize with an RNA transcribed from the locus in the targeted population so as to form a contiguous double stranded RNA for interacting with PKR. The activation of PKR gives rise to selective cell death in the targeted population.

L'invention concerne des procédés et compositions nouveaux destinés à provoquer la mort sélective de cellules, par activation de la protéine kinase PKR. Dans un mode de réalisation préféré, l'invention concerne un procédé destiné à provoquer la mort de cellules dans une population ciblée de cellules, ce procédé comprenant les étapes suivantes consistant: à choisir une séquence nucléotidique, présente dans la population ciblée, au niveau d'un seul locus génétique, et absente au niveau du locus équivalent, dans une population de cellules non ciblées, à obtenir au moins un ARN antisens possédant une homologie de séquence avec le locus, dans la population ciblée, à permettre à cet ARN antisens de s'hybrider avec un ARN transcrit à partir du locus, dans la population ciblée, de manière à former un ARN à deux brins contigus destinés à interagir avec la protéine kinase PKR. L'activation de cette protéine provoque la mort sélective de cellules dans la population ciblée.

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