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Polymersoligonucleotide, or polymer-oligonucleotide conjugate, is a class of macromolecules in which oligonucleotide sequences are covalently linked to a polymer backbone, or oligonucleotide units are integrated into the polymer chain. This combination aims to merge sequence-specific nucleic acid recognition with the physical properties of polymers, such as solubility, stability, and controlled release. The term is used in contexts including diagnostics, therapeutics, and nanoscale engineering.

Form and synthesis: The oligonucleotide can be attached as side chains (grafted conjugates) or incorporated as part of the polymer backbone. Common synthesis routes include post-polymerization functionalization with click chemistry (for example, azide-alkyne cycloaddition) or NHS-ester coupling, and, less commonly, copolymerization with nucleic acid–bearing monomers. Protecting groups and orthogonal chemistries enable selective attachment and sequence control. Polymer backbones vary and may include poly(ethylene glycol), polyacrylates, polyesters, or dendritic structures designed to improve biocompatibility and delivery properties.

Properties and applications: The conjugation confers multivalency and potential nuclease resistance when using modified nucleotides, alongside enhanced pharmacokinetics. Applications span nucleic acid diagnostics (sensors and reporters), therapeutic modalities such as antisense or RNA interference delivery, and nanoscale devices where polymers provide scaffolding and stability. Challenges include synthesis complexity, potential immunogenicity, and balancing flexibility with the accessibility of the oligonucleotide sequences for hybridization.

Related concepts include polymer-oligonucleotide conjugates and DNA-polymer conjugates, which describe similar integrations of nucleic acid units with polymeric frameworks.