Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes
View Patent ↗The invention relates to the therapeutic use of oligonucleotides or oligonucleotide analogs as immunostimulatory agents in immunotherapy applications. The invention provides methods for enhancing the immune response caused by immunostimulatory oligonucleotide compounds.
1. An isolated immunostimulatory oligonucleotide compound, comprising an immunostimulatory dinucleotide of formula C*pG, wherein the immunostimulatory oligonucleotide compound is at least 6 nucleotides in length, and wherein C* is a cytidine analog selected from the group consisting of 5-hydroxycytosine, 5-hydroxymethylcytosine, N4-alkylcytosine and 4-thiouracil, G is guanosine, 2′-deoxyguanosine, or a guanosine analog, and p is an internucleotide linkage selected from the group consisting of phosphorothioate, and phosphorodithioate.
2. The immunostimulatory oligonucleotide compound of claim 1 , wherein C* is 5-hydroxycytosine.
3. The immunostimulatory oligonucleotide compound of claim 1 , wherein C* is 5-hydroxymethylcytosine.
4. The immunostimulatory oligonucleotide compound of claim 1 , wherein C* is N4-alkylcytosine.
5. The immunostimulatory oligonucleotide compound of claim 1 , wherein C* is 4-thiouracil.