Kinetics and dynamics of oligonucleotide hybridization

The hybridization of short nucleic acid strands is a remarkable spontaneous process that is foundational to biotechnology and nanotechnology and plays a crucial role in gene expression, editing and DNA repair. Decades of research into the mechanism of hybridization have resulted in a deep understanding of its thermodynamics, but many questions remain regarding its kinetics and dynamics. Recent advances in experiments and molecular dynamics simulations of nucleic acids are enabling more direct insight into the structural dynamics of hybridization, which can test long-standing assumptions regarding its mechanism. In this Review, we summarize the current state of knowledge of hybridization kinetics, discuss the barriers to a molecular description of hybridization dynamics, and highlight the new approaches that have begun uncovering the dynamics of hybridization and the duplex ensemble. The kinetics and dynamics of hybridization are highly sensitive to the composition of nucleic acids, and we emphasize recent discoveries and open questions on the role of nucleobase sequence and chemical modifications. This Review summarizes the current state of knowledge of DNA and RNA oligonucleotide hybridization kinetics, discusses new insights into the dynamics of hybridization and the duplex, and highlights strategies to probe hybridization at a deeper molecular level.