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Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid

View ORCID ProfileMargaret J. Lange, Donald H. Burke, John C. Chaput
doi: https://doi.org/10.1101/401612
Margaret J. Lange
1Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO
2Bond Life Sciences Center, University of Missouri, Columbia, MO
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  • ORCID record for Margaret J. Lange
Donald H. Burke
1Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, MO
2Bond Life Sciences Center, University of Missouri, Columbia, MO
3Department of Biochemistry, University of Missouri, Columbia, MO
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John C. Chaput
4Department of Pharmaceutical Sciences, University of California, Irvine, CA
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Abstract

Recent advances in synthetic biology have led to the development of nucleic acid polymers with backbone structures distinct from those found in nature, termed xeno-nucleic acids (XNAs). Several unique properties of XNAs make them attractive as nucleic acid therapeutics, most notably their high resistance to serum nucleases and ability to form Watson-Crick base-pairing with DNA and RNA. The ability of XNAs to induce immune responses has not been investigated. Threose nucleic acid (TNA), a type of XNA, is recalcitrant to nuclease digestion and capable of undergoing Darwinian evolution to produce high affinity aptamers; thus, TNA is an attractive candidate for diverse applications, including nucleic acid therapeutics. Here, we evaluated a TNA oligonucleotide derived from a CpG oligonucleotide sequence known to activate TLR9-dependent immune signaling in B cell lines. We observed a slight induction of relevant mRNA signals, robust B cell line activation, and negligible effects on cellular proliferation.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 28, 2018.
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Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid
Margaret J. Lange, Donald H. Burke, John C. Chaput
bioRxiv 401612; doi: https://doi.org/10.1101/401612
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Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid
Margaret J. Lange, Donald H. Burke, John C. Chaput
bioRxiv 401612; doi: https://doi.org/10.1101/401612

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