DNA Framework‐Engineered Long‐Range Electrostatic Interactions for DNA Hybridization Reactions

Long‐range electrostatic interactions beyond biomolecular interaction interfaces have not been extensively studied due to the limitation in engineering electric double layers in physiological fluids. Here we find that long‐range electrostatic interactions play an essential role in kinetic modulation of DNA hybridizations. Protein and gold nanoparticles with different charges are encapsulated in tetrahedral frameworks to exert diverse electrostatic effects on site‐specifically tethered single DNA strands. Using this strategy, we have successfully modulated the hybridization kinetics in both bulk solution and single molecule level. Experimental and theoretical studies reveal that long‐range Coulomb interactions are the key factor for hybridization rates. This work validates the important role of long‐range electrostatic forces in nucleic acid‐biomacromolecule complexes, which may encourage new strategies of gene regulation, antisense therapy, and nucleic acid detection. DNA frameworks contained various guest particles with different surface charges were employed to exert diverse long‐range electrostatic effects on site‐specifically tethered single stranded DNA. Long‐range Coulomb interactions are the key factor for determining the hybridization rate of the tethered DNA to its complementary sequence.