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

Lange, M. J.; Burke-Aguero, D. H.; Chaput, J.

doi:10.1101/401612

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bioRxiv · 10.1101/401612

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

Lange, M. J.·Burke-Aguero, D. H.·Chaput, J.

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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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Lange, M. J., Burke-Aguero, D. H., Chaput, J.. 2018-08-28. Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid.. https://doi.org/10.1101/401612

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