Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides

Synthetic oligodeoxynucleotides that can down-regulate cellular elements of the immune system have been developed and are being widely studied in preclinical models. These agents vary in sequence, mechanism of action, and cellular target(s) but share the ability to suppress a plethora of inflammatory responses. This work reviews the types of immunosuppressive oligodeoxynucleotide (Sup ODN) and compares their therapeutic activity against diseases characterized by pathologic levels of immune stimulation ranging from autoimmunity to septic shock to cancer (see graphical abstract). The mechanism(s) underlying the efficacy of Sup ODN and the influence size, sequence and nucleotide backbone on function are considered.

Immunotherapeutic activity of Suppressive ODNs. Broadly acting Suppressive ODN A151 ameliorates symptoms of many inflammatory and autoimmune diseases (shown in red). TLR specific Suppressive ODNs have more limited therapeutic utility (shown in blue).Figure optionsDownload high-quality image (135 K)Download as PowerPoint slide