XNAbinding

XNAbinding is the study of molecular recognition and binding interactions involving xenonucleic acids (XNA), a class of synthetic genetic polymers designed to extend or modify the information storage properties of natural DNA and RNA. The field examines how XNAs form base pairs with themselves and with natural nucleic acids, as well as how XNAs interact with proteins, enzymes, and other biomolecules. Researchers explore the chemical diversity of XNA backbones and bases to understand binding specificity, affinity, kinetics, and compatibility with biological systems.

XNA chemistries include various backbones such as threose nucleic acid (TNA), hexitol nucleic acid (HNA), and other XNAs that have been described in the literature. XNAbinding studies address cross-recognition between XNAs and natural nucleic acids, the design of XNA aptamers that selectively bind targets, and XNA–protein interactions that influence replication, transcription, and catalysis. A central aim is to achieve robust binding in physiological conditions while preserving specificity and orthogonality to native nucleic acids.

Techniques used to study XNAbinding include measurements of binding affinity via surface plasmon resonance, isothermal titration calorimetry, and gel shift assays; structural methods such as X-ray crystallography and nuclear magnetic resonance; and selection approaches adapted from SELEX to generate high-affinity XNA binders. Progress in engineered polymerases and replication systems also supports amplification and evolution of XNAs, enabling higher-throughput binding studies.

Applications of XNAbinding research span therapeutics, diagnostics, and nanotechnology. XNA aptamers and antisense XNAs can offer nuclease resistance and improved stability, enabling diagnostic assays and biosensors that function in complex biological samples. Ongoing challenges include scalable synthesis of diverse XNAs, achieving efficient enzymatic processing in cells, potential immunogenicity, and regulatory considerations for clinical use.

See also: xenonucleic acids, XNA, aptamers, SELEX, PNA, LNA, HNA, nucleic acid binding.