Methylated immunostimulatory oligonucleotides and methods of using the same
First Claim
1. A lipid-methylated nucleic acid formulation for stimulating an immune response in an animal, said formulation comprising a lipid component and a nucleic acid component comprising a methylated nucleic acid sequence.
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Abstract
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.
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Citations
44 Claims
- 1. A lipid-methylated nucleic acid formulation for stimulating an immune response in an animal, said formulation comprising a lipid component and a nucleic acid component comprising a methylated nucleic acid sequence.
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4. An adjuvant comprising a lipid-nucleic acid (LNA) formulation, wherein said LNA formulation comprises:
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a) a lipid component comprising at least one cationic lipid; and
b) a nucleic acid component comprising at least one methylated oligonucleotide;
wherein said adjuvant is capable of stimulating dendritic cells in vivo in response to antigenic stimulation. - View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12, 13)
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14. A vaccine comprising a lipid-nucleic acid (LNA) formulation in combination with at least one target antigen, wherein said at least one target antigen is mixed with or associated with said LNA formulation, said formulation comprising:
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a) a lipid component comprising at least one cationic lipid; and
b) a nucleic acid component comprising at least one methylated oligonucleotide, wherein said vaccine is capable of stimulating dendritic cells in vivo in response to presentation of said at least one target antigen by said formulation to antigen-presenting cells. - View Dependent Claims (15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28)
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26. A method for stimulating an enhanced host immune response to antigenic stimulation comprising administering to said host a lipid-nucleic acid (LNA) formulation, said LNA formulation comprising:
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a) a lipid component comprising at least one cationic lipid; and
b) a nucleic acid component comprising at least one methylated oligonucleotide;
wherein said LNA formulation is capable of stimulating dendritic cells in vivo in response to antigenic stimulation. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37)
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- 38. A method for stimulating dendritic cells, comprising contacting at least one dendritic cell with a lipid-methylated nucleic acid formulation comprising a lipid component and a nucleic acid component comprising a methylated nucleic acid sequence.
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39. A method for stimulating host dendritic cells in vivo, comprising administering to said host a lipid-methylated nucleic acid formulation comprising a lipid component and a nucleic acid component comprising a methylated nucleic acid sequence, wherein said formulation is capable of stimulating dendritic cells in vivo in response to antigenic stimulation.
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44. A method for simultaneously delivering antigenic and adjuvant immune stimulation to antigen presenting cells, comprising the administration of a lipid-nucleic acid (LNA) formulation associated with a target antigen, said LNA formulation comprising:
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a) a lipid component comprising at least one cationic lipid; and
b) a nucleic acid component comprising at least one oligonucleotide having at least one CpG dinucleotide;
wherein said LNA formulation is capable of stimulating dendritic cells in vivo.
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Specification