Dynamic and Reversible Decoration of DNA‐Based Scaffolds
Nada Farag, Milan Đorđević, Erica Del Grosso, Francesco Ricci
Abstract
An approach to achieving dynamic and reversible decoration of DNA-based scaffolds is demonstrated here. To do this, rationally engineered DNA tiles containing enzyme-responsive strands covalently conjugated to different molecular labels are employed. These strands are designed to be recognized and degraded by specific enzymes (i.e., Ribonuclease H, RNase H, or Uracil DNA Glycosylase, UDG) inducing their spontaneous de-hybridization from the assembled tile and replacement by a new strand conjugated to a different label. Multiple enzyme-responsive strands that specifically respond to different enzymes allow for dynamic, orthogonal, and reversible decoration of the DNA structures. As a proof-of-principle of the strategy, the possibility to orthogonally control the distribution of different labels (i.e., fluorophores and small molecules) on the same scaffold without crosstalk is demonstrated. By doing so, DNA scaffolds that display different antibody recognition patterns are obtained. The approach offers the possibility to control the decoration of higher-order supramolecular assemblies (including origami) with several functional moieties to achieve functional biomaterials with improved adaptability, precision, and sensing capabilities.