Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides

Pharmacol Res. 2016 Mar:105:216-25. doi: 10.1016/j.phrs.2015.11.010. Epub 2016 Jan 15.

Abstract

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.

Keywords: CpG oligonucleotide; Dendritic cell; IRF5; IRF8; TLR9.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Humans
  • Immunosuppressive Agents / chemistry*
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Interferon Regulatory Factors / immunology
  • Oligodeoxyribonucleotides / chemistry*
  • Oligodeoxyribonucleotides / pharmacology
  • Oligodeoxyribonucleotides / therapeutic use*
  • Toll-Like Receptor 9 / immunology

Substances

  • Immunosuppressive Agents
  • Interferon Regulatory Factors
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9