Multiplexed sequence-resolved screening of transient DNA hybridization for programmable nanotechnology
DNA-based technologies rely on short, transient hybridization events, but selecting sequences with desired kinetic properties remains largely empirical because hybridization kinetics are difficult to predict from sequence and slow to measure one sequence at a time. Here, we introduce SPARXS-Hyb, an implementation of SPARXS (Single-molecule Parallel Analysis for Rapid eXploration of Sequence…
DNA-based technologies depend on short, temporary hybridization events, but pinpointing sequences with desired kinetic properties is often done through trial and error. The process is challenging as hybridization kinetics cannot be accurately predicted from sequence alone and is time-consuming when tested one sequence at a time.
Introducing SPARXS-Hyb, a method that builds on SPARXS (Single-molecule Parallel Analysis for Rapid eXploration of Sequence space), researchers have developed a new way to efficiently screen DNA hybridization. By utilizing a surface-immobilized docking-strand library and a quencher-labelled imager-strand library, SPARXS-Hyb can assess the kinetic properties of 128 different DNA sequences within a single measurement.
This groundbreaking approach eliminates the confounding factor of sequential measurements and allows for direct comparisons of sequence-dependent variations. The team's findings shed light on transient binding behaviors, and reveal a sequence that allows for a tenfold increase in sampling rate in DNA-PAINT, a super-resolution microscopy technique based on DNA hybridization.
By enabling multiplexed screening of a sequence library, SPARXS-Hyb offers a promising path to kinetics-guided sequence selection for programmable transient interactions in DNA nanotechnology.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
