High‐Affinity Host–Guest Recognition for Efficient Assembly and Enzymatic Responsiveness of DNA Nanostructures

Abstract

The combination of multiple orthogonal interactions enables hierarchical complexity in self‐assembled nanoscale materials. Here, efficient supramolecular polymerization of DNA origami nanostructures is demonstrated using a multivalent display of small molecule host–guest interactions. Modification of DNA strands with cucurbit[7]uril (CB[7]) and its adamantane guest, yielding a supramolecular complex with an affinity of order 1010 m−1, directs hierarchical assembly of origami monomers into 1D nanofibers. This affinity regime enables efficient polymerization; a lower‐affinity β‐cyclodextrin–adamantane complex does not promote extended structures at a similar valency. Finally, the utility of the high‐affinity CB[7]–adamantane interactions is exploited to enable responsive enzymatic actuation of origami nanofibers assembled using peptide linkers. This work demonstrates the power of high‐affinity CB[7]–guest recognition as an orthogonal axis to drive self‐assembly in DNA nanotechnology.

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications

“…In addition, high-affinity ADA/CB[n] interaction between functionalized DNA strands could direct hierarchical assembly of origami monomers into DNA nanofibers of micrometer-length. 294 As another fascinating example of bioapplicable nanomaterial important for understanding and diagnosing The supramolecular system was constructed with ADA and CB [7] functionalized with luminol and AIEgen, respectively, using the resulting host-guest interactions to produce efficient bioluminescence resonance energy transfer (BRET) from blue-emissive luminol to red-emissive AIEgen, thus providing fluorescent imaging. 266 In the end, we will present one recent example of AuNPs combined with a different host-guest ADA/CB[n] supramolecular system that was developed for quantitative detection of SARS-CoV-2 antibodies in human serum.…”

“…In addition, high-affinity ADA/CB[ n ] interaction between functionalized DNA strands could direct hierarchical assembly of origami monomers into DNA nanofibers of micrometer-length. 294 …”

Purification of DNA Nanoparticles Using Photocleavable Biotin Tethers

“…At the turn of 2023, a series of preliminary reports demonstrated that gene-encoded synthetic deoxyribonucleic acid (DNA) nanoparticles (NPs) can enable protein expression via transcription and translation in vitro and in vivo. Simultaneously, custom DNA origami NPs with multiple enzymatically encoded functional modifications are gaining traction for biomedical applications. − In these rapidly growing nanoscale applications of synthetic DNA origami NPs, the role of the scaffold strandwhich is the long single-stranded template DNA (ssDNA) within these particleshas become multifaceted. The traditional DNA origami NPsmade predominantly with scaffolds sourced from bacteriophage’s canonical genomic ssDNAsare still widely applied in single molecular studies, photonics, plasmonic, and biomedical applications, but a new suite of DNA NPs leverage nonviral sequences as scaffold strands to serve functional roles. ,− These scaffold strands are produced by enzymes (such as asymmetric polymerase chain reaction (aPCR)) by separating ssDNA from double-stranded DNA (dsDNA) or phage-based methods, often requiring purification .…”