Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)

Research output: Contribution to journalJournal articlepeer-review

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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 journalJournal articlepeer-review

Harvard

Vollmer, J, Uhlmann, E, Stenvang, J, Schetter, C, Jurk, M, Wader, T, Wüllner, M & Krieg, AM 2004, 'Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)', Oligonucleotides, vol. 14, no. 1, pp. 23-31. https://doi.org/10.1089/154545704322988021

APA

Vollmer, J., Uhlmann, E., Stenvang, J., Schetter, C., Jurk, M., Wader, T., Wüllner, M., & Krieg, A. M. (2004). Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA). Oligonucleotides, 14(1), 23-31. https://doi.org/10.1089/154545704322988021

Vancouver

Vollmer J, Uhlmann E, Stenvang J, Schetter C, Jurk M, Wader T et al. Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA). Oligonucleotides. 2004;14(1):23-31. https://doi.org/10.1089/154545704322988021

Author

Vollmer, Jörg ; Uhlmann, Eugen ; Stenvang, Jan ; Schetter, Christian ; Jurk, Marion ; Wader, Tanja ; Wüllner, Meike ; Krieg, Arthur M. / Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA). In: Oligonucleotides. 2004 ; Vol. 14, No. 1. pp. 23-31.

Bibtex

@article{1f5cd609492f4857ada09cf5050d87a2,
title = "Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)",
abstract = "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.",
keywords = "Cells, Cultured, CpG Islands, Cytokines, Enzyme-Linked Immunosorbent Assay, Humans, Oligodeoxyribonucleotides",
author = "J{\"o}rg Vollmer and Eugen Uhlmann and Jan Stenvang and Christian Schetter and Marion Jurk and Tanja Wader and Meike W{\"u}llner and Krieg, {Arthur M}",
year = "2004",
doi = "10.1089/154545704322988021",
language = "English",
volume = "14",
pages = "23--31",
journal = "Nucleic Acid Therapeutics",
issn = "2159-3337",
publisher = "Mary AnnLiebert, Inc. Publishers",
number = "1",

}

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