IMMUNOSTIMULATION BY CHEMICALLY MODIFIED RNA
The present invention relates to an immunostimulating agent comprising at least one chemically modified RNA. The invention furthermore relates to a vaccine which comprises at least one antigen in combination with the immunostimulating agent. The immunostimulating agent according to the invention and the vaccine according to the invention are employed in particular against infectious diseases or cancer diseases.
1 . Use of a single-stranded RNA comprising at least one chemical modification, wherein the chemical modification is a 5′ cap structure, for the preparation of an immunostimulating agent.
2 . Use according to claim 1 , characterized in that the 5′ cap structure is selected from m7G(5′)ppp, (5′)A,G(5′)ppp(5′)A and G(5′)ppp(5′)G.
3 . Use according to claim 1 , characterized in that at least one nucleotide of the RNA is an analogue of naturally occurring nucleotides.
4 . Use according to claim 3 , characterized in that the RNA consists of nucleotide analogues.
5 . Use according to claim 3 , characterized in that the analogue is selected from the group consisting of phosphorothioates, phosphoroamidates, peptide nucleotides, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine.
6 . Use according to claim 5 , characterized in that the analogue is a phosphorothioate.
7 . Use according to claim 6 , characterized in that the RNA consists of 2 to about 1.000 nucleotides.
8 . Use according to claim 1 , characterized in that the RNA is associated or complexed with a polycationic compound.
9 . Use according to claim 8 , characterized in that the polycationic compound is protamine.
10 . Use according to claim 1 , characterized in that the immunostimulating agent comprises at least one adjuvant.
11 . Use according to claim 10 , characterized in that the adjuvant is selected from the group consisting of cytokines, lipopeptides and CpG oligonucleotides.
12 . Use according to claim 1 , furthermore comprising a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable vehicle.
13 . Use according to claim 1 for the prevention and/or treatment of infectious diseases or cancer diseases.
14 . Vaccine containing a single-stranded RNA comprising at least one chemical modification, wherein the chemical modification is a 5′ cap structure, and at least one antigen.
15 . Vaccine according to claim 14 , characterized in that the antigen is selected from the group consisting of peptides, polypeptides, cells, cell extracts, polysaccharides, polysaccharide conjugates, lipids, glycolipids and carbohydrates.
16 . Vaccine according to claim 15 , characterized in that the peptide antigen or polypeptide antigen is in the form of a nucleic acid which codes for this.
17 . Vaccine according to claim 16 , characterized in that the nucleic acid is an mRNA.
18 . Vaccine according to claim 17 , characterized in that the mRNA is stabilized and/or translation-optimized.
19 . Vaccine according to claim 14 , characterized in that the antigen is selected from tumour antigens and antigens of viruses, bacteria, fungi and protozoa.
20 . Vaccine according to claim 19 , characterized in that the viral, bacterial, fungal or protozoological antigen originates from a secreted protein.
21 . Vaccine according to claim 19 , characterized in that the antigen is a polyepitope of tumour antigens or antigens of viruses, bacteria, fungi or protozoa.
22 . Use of a vaccine according to claim 14 for vaccination against infectious diseases or cancer diseases.