A novel class of immune-stimulatory CpG oligodeoxynucleotides unifies high potency in type I interferon induction with preferred structural properties

Oligonucleotides. 2010 Apr;20(2):93-101. doi: 10.1089/oli.2009.0210.

Abstract

Unmethylated deoxycytidyl-deoxyguanosin dinucleotide (CpG)-containing oligodeoxynucleotides (ODNs) have been well characterized as agonists for Toll-like receptor 9. We here describe a new class of CpG ODNs, the so-called P-Class, which combines preferred properties of known CpG ODN classes. This P-Class contains two palindromic sequences, enabling it to form concatamers, multimeric units, where each molecule is bound via Watson-Crick basepairing to a second and a third palindrome. The type I interferon-inducing potency and efficacy of the double-palindromic P-Class ODN is substantially higher than that of previously described C-Class ODNs, and they stimulate superior cytokine production upon in vivo application. The multimeric structures of the P-Class can be resolved to monomers and dimers by formulation in low-salt buffer, retaining the strong and potent immune effects. Taken together, we have discovered a novel class of CpG ODNs, the P-Class, with promising superior activity for disease application.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chromatography, Gel
  • CpG Islands*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immune System / drug effects*
  • Interferon Type I / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / pharmacology*

Substances

  • Interferon Type I
  • Oligodeoxyribonucleotides