The Design and StructureFunctional Properties of DNA-Based Immunomodulatory Sequences

DNA-based immunomodulatory sequences (DIMS) are promising compounds for the treatment of different diseases, including inflammation and cancer. They act through the interaction with TLR9, a member of the Toll-like receptor family whose essential role in innate immunity was recently recognised by being awarded the Nobel Prize 2011. Combining the data obtained from in vitro and in vivo models with circular dichroism spectroscopy approach, we could show that formation of certain tertiary structures by DIMS can be connected to their specific physiologic effects such as activation of immune cells, induction of interferons and delay of the disease progression. Moreover the ability of selected DIMS compounds to form certain tertiary structures must be regarded as important for biological activities as is the presence of functional primary structure motifs such as unmethylated deoxyribodinucleotide CpG. These findings are useful when considering the design of DNA-based immunomodulators.