A novel class of immune-stimulatory CpG oligodeoxynucleotides unifies high potency in type I interferon induction with preferred structural properties.
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.
Samulowitz
Ulrike
U
Coley Pharmaceutical GmbH--A Pfizer Company, Düsseldorf, Germany.
Weber
Markus
M
Weeratna
Risini
R
Uhlmann
Eugen
E
Noll
Bernhard
B
Krieg
Arthur M
AM
Vollmer
Jörg
J
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002850:Chromatography, Gel; D018899:CpG Islands; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007370:Interferon Type I / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*
D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides