Chimeric XNA: An Unconventional Design for Orthogonal Informational Systems

The paradigm of homogenous-sugar-backbone of RNA and DNA has reliably guided the construction of many functional and useful xeno nucleic acid (XNA) systems to date. Deviations from this monotonous and canonical design, in many cases, results in oligonucleotide systems that lack base pairing with themselves, or with RNA or DNA. Here we show that nucleotides of two such compromised XNA systems can be combined with RNA and DNA in specific patterns to produce chimeric-backbone oligonucleotides, which in certain cases demonstrate base pairing properties comparable to—or stronger than—canonical systems, while also altering the conventional Watson–Crick pairing behavior. The unorthodox pairing properties generated from these chimeric sugar-backbone oligonucleotides suggest a counterintuitive approach of creating modules consisting of non-base pairing XNAs with RNA/DNA in a set pattern. This strategy has the potential to increase the diversity of unconventional nucleic acids leading to orthogonal backbone-sequence-controlled informational systems.