Synthetic oligoribonucleotides containing arabinonucleotides act as agonists of TLR7 and 8.
In continuation of our studies with stabilized immune modulatory RNA (SIMRA) compounds, we have synthesized novel SIMRA compounds incorporating arabinonucleotides to study their effects on TLR7 and TLR8 activation. The SIMRA compounds containing ara-G, ara-C, ara-U or ara-A substitutions activated TLR8 in HEK293 cells. Interestingly, the SIMRA compound containing ara-C also activated TLR7 and stimulated immune responses in vivo in mice. In human PBMC and pDC assays, SIMRA compounds containing arabinonucleotides induced Th1-type cytokine profiles. These results suggest that SIMRA compounds containing arabinonucleotides act as agonists of TLR7 and TLR8.
Lan
Tao
T
Idera Pharmaceuticals, Inc., 167 Sidney Street, Cambridge, MA 02139, United States.
Bhagat
Lakshmi
L
Wang
Daqing
D
Dai
Meiru
M
Kandimalla
Ekambar R
ER
Agrawal
Sudhir
S
D000818:Animals; D001088:Arabinonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D001483:Base Sequence; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009843:Oligoribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism
D001088:Arabinonucleotides; D016207:Cytokines; D009843:Oligoribonucleotides; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8