D. Yu et al., Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages, BIO MED CH, 9(11), 2001, pp. 2803-2808
Bacterial DNA and synthetic oligodeoxynuelcotides containing unmethylated C
pG-motifs in a particular sequence context activate vertebrate immune cells
. We examined the significance of negatively charged internucleoside linkag
es in the flanking sequences 5' and 3' to the CpG-motif on immunostimulator
y activity. Cell proliferation and secretion of IL-12 and IL-6 in mouse spl
een cell cultures, and spleen weights of mice increased significantly when
a non-ionic linkage was placed at least four or more internucleoside linkag
es away from the CpG-motif in the 5'-flanking sequence. When the non-ionic
linkage was placed closer than three internucleoside linkages in the 5'-fla
nking sequence to the CpG-motif, immunostimulatory activity was suppressed
compared with that observed with the unmodified parent oligo. In general, t
he placement of non-ionic linkage in the 3'-flanking sequence to the CpG-mo
tif either did not affect or slightly increased immunostimulatory activity
compared with the parent oligo. These results have significance in understa
nding CpG oligonucleotide-receptor interactions and the development of pote
nt immunomodulatory agents. (C) 2001 Elsevier Science Ltd. All rights reser
ved.