Stimulation of the Immune System by Therapeutic Antisense Oligodeoxynucleotides and Small Interfering RNAs via Nucleic Acid Receptors How to Avoid Immune Activation

Most of the therapeutic applications for synthetic oligodeoxynucleotides (ODN) and oligoribonucleotides (ORN) relate to mechanisms of manipulating gene expression based on Watson-Crick base pairing to endogenous nucleic acids. However, in recent years it has become apparent that the immune system has evolved defense mechanisms against infections that are based on the detection of infecting viral and bacterial nucleic acids. In some cases, synthetic ODN and ORN can trigger these defenses and, therefore, can interfere with or distort the mechanism of action of antisense ODN or small interfering RNAs.