| Popis: |
In recent years a number of innate immune receptors, such as retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), absent in melanoma 2 (AIM2)-like receptors (ALRs), stimulator of interferon genes (STING), nucleotide oligomerization domain (NOD)-like receptors, and Toll-like receptors (TLRs), which recognize exogenous and endogenous nucleic acid molecular patterns, have been discovered. This chapter is focused on the chemistry of oligonucleotides which recognize and modulate immune responses specifically through TLRs 3, 7, 8, and 9. These TLRs are expressed in endosomes of many cells of the immune system. Known ligands of these receptors include viral double-stranded RNA for TLR3, viral single-stranded RNA for TLR7 and TLR8, and bacterial and viral DNA containing unmethylated CpG motifs for TLR9. Structure–activity relationship studies of synthetic oligonucleotides, with the goal of creating novel agonists of TLR3, 7, 8, and 9, have been conducted to modulate immune responses mediated through targeted receptors. Preclinical proof of concept studies of agonists of TLR3, 7, 8, and 9 for various diseases have been reported. A number of TLR9-agonist candidates have advanced to clinical trials, including for treatment of cancers, allergies, asthma, and infectious diseases, and also as adjuvants with vaccines. Recently, a hepatitis B (HepB) vaccine containing a TLR9 agonist as an adjuvant has been approved. |
