Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)
Research output: Contribution to journal › Journal article › peer-review
Standard
Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA). / Vollmer, Jörg; Uhlmann, Eugen; Stenvang, Jan; Schetter, Christian; Jurk, Marion; Wader, Tanja; Wüllner, Meike; Krieg, Arthur M.
In: Oligonucleotides, Vol. 14, No. 1, 2004, p. 23-31.Research output: Contribution to journal › Journal article › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)
AU - Vollmer, Jörg
AU - Uhlmann, Eugen
AU - Stenvang, Jan
AU - Schetter, Christian
AU - Jurk, Marion
AU - Wader, Tanja
AU - Wüllner, Meike
AU - Krieg, Arthur M
PY - 2004
Y1 - 2004
N2 - Locked nucleic acid (LNA) is an RNA derivative that when introduced into oligodeoxynucleotides (ODN), mediates high efficacy and stability. CpG ODNs are potent immune stimulators and are recognized by toll-like receptor-9 (TLR9). Some phosphorothioate antisense ODNs bearing CpG dinucleotides have been shown to possess immune modulatory capacities. We investigated the effects of LNA substitutions on immune stimulation mediated by antisense ODN G3139 or CpG ODN 2006. LNA ODNs were tested for their ability to stimulate cytokine secretion from human immune cells or TLR9-dependent signaling. Phosphorothioate chimeric LNA/DNA antisense ODNs with phosphodiester-linked LNA nucleobases at both ends showed a marked decrease of immune modulation with an increasing number of 3' and 5' LNA bases. In addition, guanosine-LNA and cytosine-LNA or simply cytosine-LNA substitutions in the CpG dinucleotides of ODN 2006 led to strong decrease or near complete loss of immune modulation. TLR9-mediated signaling was similarly affected. These data indicate that increasing amounts of LNA residues in the flanks or substitutions of CpG nucleobases with LNA reduce or eliminate the immune stimulatory effects of CpG-containing phosphorothioate ODN.
AB - Locked nucleic acid (LNA) is an RNA derivative that when introduced into oligodeoxynucleotides (ODN), mediates high efficacy and stability. CpG ODNs are potent immune stimulators and are recognized by toll-like receptor-9 (TLR9). Some phosphorothioate antisense ODNs bearing CpG dinucleotides have been shown to possess immune modulatory capacities. We investigated the effects of LNA substitutions on immune stimulation mediated by antisense ODN G3139 or CpG ODN 2006. LNA ODNs were tested for their ability to stimulate cytokine secretion from human immune cells or TLR9-dependent signaling. Phosphorothioate chimeric LNA/DNA antisense ODNs with phosphodiester-linked LNA nucleobases at both ends showed a marked decrease of immune modulation with an increasing number of 3' and 5' LNA bases. In addition, guanosine-LNA and cytosine-LNA or simply cytosine-LNA substitutions in the CpG dinucleotides of ODN 2006 led to strong decrease or near complete loss of immune modulation. TLR9-mediated signaling was similarly affected. These data indicate that increasing amounts of LNA residues in the flanks or substitutions of CpG nucleobases with LNA reduce or eliminate the immune stimulatory effects of CpG-containing phosphorothioate ODN.
KW - Cells, Cultured
KW - CpG Islands
KW - Cytokines
KW - Enzyme-Linked Immunosorbent Assay
KW - Humans
KW - Oligodeoxyribonucleotides
U2 - 10.1089/154545704322988021
DO - 10.1089/154545704322988021
M3 - Journal article
C2 - 15104893
VL - 14
SP - 23
EP - 31
JO - Nucleic Acid Therapeutics
JF - Nucleic Acid Therapeutics
SN - 2159-3337
IS - 1
ER -
ID: 59325090