Controllable DNA hybridization by host-guest complexation-mediated ligand invasion

Area of Science:

• Supramolecular Chemistry
• Nucleic Acid Chemistry
• Nanotechnology

Background:

• Dynamic control of nucleic acid hybridization is crucial for developing switchable nanostructures and controllable functionalities.
• Existing methods for regulating DNA interactions often lack orthogonality and reversibility.

Purpose of the Study:

• To introduce a novel ligand-invasion pathway for regulating DNA hybridization based on host-guest interactions.
• To demonstrate orthogonal and reversible control over DNA duplex dissociation and recovery.
• To apply this strategy for functional regulation of nucleic acid-based systems.

Main Methods:

• Utilized cucurbit[7]uril as an invading ligand and nucleobase-integrated guest molecules as recognition handles.
• Disrupted Watson-Crick base pairing through ligand binding to induce DNA duplex dissociation.
• Applied the ligand-invasion strategy to regulate an RNA-cleaving DNAzyme and an antisense oligonucleotide in living cells.

Main Results:

• Achieved orthogonal and reversible manipulation of DNA duplex dissociation and recovery.
• Successfully demonstrated the functional regulation of a DNAzyme and an antisense oligonucleotide using the ligand-invasion approach.
• Established a general pathway for dynamic control of nucleic acid structures and functionalities.

Conclusions:

• The ligand-invasion strategy provides a versatile method for dynamic control of nucleic acid hybridization.
• This approach enables precise manipulation of DNA structures and functionalities through supramolecular interactions.
• Opens new avenues for designing responsive nucleic acid-based materials and therapeutics.