Identification of DNA Sequence Motifs that Suppress the Immune Response to CpG DNA
This invention claims compositions and methods for suppressing CpG oligonucleotide immunostimulatory action with suppressive motifs comprising mammalian DNA. The sequences of the suppressive motifs claimed in the application comprise multimeric repeats, which have a tendency to form "G-tetrads," which suppress CpG induced immune activation. The inventors have found through in vivo and in vitro experimentation that these suppressive motifs inhibited CpG DNA induced proliferation and cytokine production. Further experimentation by the inventors has shown that ODNs containing the most said repeats were the most suppressive. There are multiple therapeutic uses for the suppressive oligodeoxynucleotides (ODNs) of the invention, such as use in the prevention or treatment of septic shock, adult respiratory distress syndrome (ARDS), or autoimmune disease. Furthermore, the inventors disclose that eliminating suppressive motifs from the plasmid backbone of DNA vaccines may improve vaccine immunogenicity by maximizing the effect of CpG motifs present in such vectors. The advantages associated with use of suppressive motifs is that therapeutics based on this technology would avoid many of the unwanted side effects associated with current immunosuppressive therapeutics.
U.S. Pat: No. 7,514,414 issued 2009-04-07
U.S. Pat: No. 8,227,438 issued 2012-07-24
U.S. Pat: No. 8,580,944 issued 2013-11-12
US Application No. 14/026,995
PCT Application No. PCT/US2002/030532
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
Silver Spring, MD 20993
OTT Reference No: E-218-2001/0
Updated: August 7, 2015