RT Journal Article
SR Electronic
T1 Activation of innate immune responses by a CpG oligonucleotide sequence composed entirely of threose nucleic acid
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 401612
DO 10.1101/401612
A1 Margaret J. Lange
A1 Donald H. Burke
A1 John C. Chaput
YR 2018
UL http://biorxiv.org/content/early/2018/08/28/401612.abstract
AB 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.