Methylated immunostimulatory oligonucleotides and methods of...

A - Human Necessities – 61 – K

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A61K 39/39 (2006.01) A61K 39/00 (2006.01) A61P 31/00 (2006.01) A61P 35/00 (2006.01) A61P 37/00 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2485400

The invention discloses that methylated nucleic acids, particularly methylated oligonucleotides, and more particularly methylated oligonucleotides bearing a methylated cytosine of a CpG dinucleotide motif can be made immunostimulatory in vivo, by encapsulation of the nucleic acid in a lipid particle. It is further disclosed that encapsulated methylated nucleic acids that are ordinarily not immunostimulatory in vivo are as effective or even more effective than their encapsulated unmethylated counterparts. Also disclosed are methods for activating and/or expanding dendritic cell populations in response to antigenic stimulation using the compositions and methods disclosed herein.

La présente invention se rapporte au fait que des acides nucléiques méthylés, particulièrement des oligonucléotides méthylés et encore plus particulièrement des oligonucléotides méthylés portant une cytosine méthylée d'un motif dinucléotide CpG peuvent être rendus immunostimulateurs in vivo, par encapsulation de l'acide nucléique dans une particule lipidique. On a également découvert que les acides nucléiques méthylés encapsulés qui ne sont ordinairement pas immunostimulateurs in vivo, sont efficaces et même plus efficaces que leurs homologues non méthylés encapsulés. Cette invention concerne également des méthodes d'activation et/ou d'extension de populations de cellules dendritiques en réponse à une stimulation antigénique au moyen des compositions et des méthodes selon l'invention.

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