5' CpG nucleic acids and methods of use

An oligonucleotide comprising:

• 5′TCGTN13′
• wherein N1 is 3-96 nucleotides, wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein N1 does not include an unmethylated cg motif and when N1 is 16 nucleotides N1 does not include a C12 and when N1 is 8 nucleotides N1 is at least 50% C or 70% T.

An oligonucleotide comprising:

• 5′TCGAN13′
• wherein N1 is 3-96 nucleotides, wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein N1 does not include an unmethylated CG motif and when N1 is 19 nucleotides N1 is at least 55% pyrimidine, and when N1 is 8 nucleotides N1 is at least 50% T or C.

An oligonucleotide comprising:

• 5′TCGN13′
• wherein N1 is 10-96 nucleotides, wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein the C content of the oligonucleotide is less than or equal to 60%, and the A content is less than or equal to 30%, and wherein N1 does not include an unmethylated CG motif.

An oligonucleotide comprising:

• 5′TYZN13′
• wherein Y is a cytosine or modified cystosine, wherein Z is a guanine or modified guanine, N1 is 4-97 nucleotides, wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, and wherein the oligonucleotide does not include an unmethylated CG motif.

An oligonucleotide comprising:

• 5′-X3CGM3-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein X3 is a single nucleotide that does not comprise a CG dinucleotide, wherein M3 is a nucleic acid of 3-27 nucleotides that is free of a CG dinucleotide, and wherein M has at least one of the following properties:
• is free of a TC dinucleotide, is at least 30% T nucleotides, consists of A, T, and G or is free of a CCTTCC hexamer having at least one modified internucleotide linkage.

An oligonucleotide comprising:

• 5′-X4CGM4-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein X4 is a dinucleotide that does not comprise a CG dinucleotide, wherein M is a nucleic acid of 2-26 nucleotides that is free of a CG dinucleotide, and wherein M4 has at least one of the following properties:
• is free of a TG or a GT dinucleotide, is at least 38% T nucleotides or consists of A and T.

An oligonucleotide comprising:

• 5′-X5CGM5-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein X5 is a trinucleotide that does not comprise a CG dinucleotide, wherein M5 is a nucleic acid of 1-25 nucleotides that is free of a CG dinucleotide, and wherein M5 has at least one of the following properties:
• is free of a CT dinucleotide and does not include at least one phosphorothioate linkage, is at least 41% T nucleotides, or consists of A and C.

An oligonucleotide comprising:

• 5′-TTGM6-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein M6 is a nucleic acid that consists of 5-21 nucleotides, wherein M does not comprise a CG dinucleotide, wherein M6 is comprised of at least 30% T nucleotides, and wherein said nucleotide is 10-24 nucleotides in length.

An oligonucleotide comprising:

• 5′-X6CGM7-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein X6 is 1-3 nucleotides and does not include a CG dinucleotide, wherein M7 is a nucleic acid of 6-27 nucleotides and includes at least three CG dinucleotides and is at least 50% T nucleotides.

An oligonucleotide comprising:

• 5‘-’ TTGM8-3′
• wherein 5′ designates the 5′ end of the oligonucleotide and 3′ designates the 3′ end of the oligonucleotide, wherein M7 is a nucleic acid of 6-18 nucleotides and includes at least one CG dinucleotide and is at least 50% T nucleotides.