title: Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides.
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.
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA; Bilkent University, Molecular Biology and Genetic Department, Therapeutic ODN Research Laboratory, Ankara, Turkey.
authors.forename: Defne
authors.initials: D
authors.lastname: Bayik
authors.affiliation: Bilkent University, Molecular Biology and Genetic Department, Therapeutic ODN Research Laboratory, Ankara, Turkey. Electronic address: ihsangursel@bilkent.edu.tr.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Gursel
authors.affiliation: Cancer and Inflammation Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. Electronic address: klinmand@mail.nih.gov.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D000818:Animals; D001483:Base Sequence; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D050835:Interferon Regulatory Factors / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051217:Toll-Like Receptor 9 / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D050835:Interferon Regulatory Factors; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9
keywords: CpG oligonucleotide; Dendritic cell; IRF5; IRF8; TLR9