The present invention relates to methods for identifying oligonucleotides capable of modulating the immune system in a mammalian subject, comprising analysis of which tertiary structural form said oligonucleotide adopts, in aqueous solution. Further, the invention provides oligonucleotides identifiable by the methods of the invention and to their use in methods of treating diseases, such as inflammatory diseases, infectious diseases, neurodegenerative diseases, autoimmune diseases and cancer.