Guanine-Rich DNA Aptamers for Selective Binding to Agarose Hydrogels

Although DNA-functionalized hydrogels have been widely explored for sensing, controlled release, and smart materials, the potential for strong, noncovalent recognition between DNA and hydrated polymer networks remains largely unexplored. Here, we report the selection of DNA aptamers that specifically bind agarose hydrogels. Using a structured DNA library and agarose beads as the target, a dominant guanine-rich sequence, Agar-1, emerged after 11 rounds of selection. Quantitative PCR and fluorescence assays confirmed that the enriched sequences bind agarose substantially more strongly than a random DNA library. Truncation yielded a 42-nucleotide aptamer that retained binding activity, whereas further truncation that preserved only the guanine-rich region abolished binding, indicating a strict structural requirement. Notably, binding required Mg2+ and was inhibited by K+, suggesting a non-G-quadruplex recognition mechanism. In contrast to previously reported C/T-rich sequences that bind microplastics, the G-rich agarose aptamers highlight the versatility of DNA-polymer interactions and demonstrate how simple changes in sequence composition can drive recognition of distinct materials. These findings establish the feasibility of evolving aptamers against hydrogels and provide a foundation for engineering programmable DNA-hydrogel interfaces for biosensing, responsive materials, and controlled-release applications.