Grafting from a Hybrid DNA–Covalent Polymer by the Hybridization Chain Reaction

[Image: see text] Nucleic acid–polymer conjugates are an attractive class of materials endowed with tunable and responsive character. Herein, we exploit the dynamic character of nucleic acids in the preparation of hybrid DNA–covalent polymers with extendable grafts by the hybridization chain reaction. Addition of DNA hairpins to an initiator DNA–dextran graft copolymer resulted in the growth of the DNA grafts as evidenced by various characterization techniques over several length scales. Additionally, aggregation of the initiator DNA–graft copolymer before the hybridization chain reaction was observed resulting in the formation of kinetically trapped aggregates several hundreds of nanometers in diameter that could be disrupted by a preheating step at 60 °C prior to extension at room temperature. Materials of increasing viscosity were rapidly formed when metastable DNA hairpins were added to the initiator DNA-dextran grafted copolymer with increasing concentration of the components in the mixture. This study shows the potential for hierarchical self-assembly of DNA-grafted polymers through the hybridization chain reaction and opens the door for biomedical applications where viscosity can be used as a readout.