Dr David Rusling, University of Portsmouth, UK

Triplex-forming oligonucleotides: a third strand for DNA (nano)technologies

Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA recognition agents that bind within the major groove of double-stranded DNA through the formation of specific base triplets, generating a triplex structure. Experiments have shown that, at least in principle, TFOs can be exploited as gene-targeting agents for the transient control of gene activity in cell culture and in vivo, as well as for the permanent alteration of gene expression through directed mutagenesis. They have also been used in vitro to detect and/or isolate plasmid and genomic DNA, as well as to introduce functionality into artificial DNA nanostructures assembled by crossover strand exchange. This seminar will discuss some of our recent efforts to improve the triplex-forming properties of oligonucleotides, as well as the steps we are making towards their use in therapy, diagnostics, and in particular, DNA nanotechnology. For example, we have been exploiting triplex recognition as means to functionalise various DNA objects, lattices, and devices. Such structures offer applications that include the organisation of nanoelectronics, the manipulation of biological or chemical cascades, and the structure determination of periodically positioned molecules by structural analysis techniques. This work has involved collaborations with Keith Fox (Southampton, UK), Tom Brown (Oxford, UK), Andrey Revyakin (Leicester), as well as the late Ned Seeman (New York, US).

Some recent highlights: Nucleic acids Res 2018, Nucleic Acids Res 2021, ACS Nano 2022, and JACS 2023.