Improving the Enzymatic Stability and the Pharmacokinetics of Oligonucleotides via DNA-Backboned Bottlebrush Polymers

Herein, we design and synthesize site-specifically PEGylated oligonucleotide hairpins and demonstrate that their ability to undergo hybridization chain reaction is nearly unaffected by the PEGylation. The resulting DNA-backboned bottlebrush polymers with PEG side chains exhibit increased resistance against nucleolytic degradation, enhanced thermal stabilities, and elevated blood retention times in vivo, which collectively pave the way for more therapeutically focused DNA nanostructure designs.