What is it about?
In DNA-RNA strand invasion (or strand displacement), double-stranded DNA is gradually replaced by a DNA-RNA hybrid, while one of the original DNA strands is forced out. Using computational modelling and experiments, we comprehensively study how base sequence affects the speeds of these processes. We find that strand displacement rate can be finely tuned using sequence.
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Why is it important?
DNA-RNA strand displacement underlies CRISPR-Cas9 gene editing, although not much attention has been given to the effect of guide RNA sequence (which participates in the strand displacement). Here we show that the speed at which DNA-RNA strand displacement proceeds strongly depends on the sequence, which potentially opens a new avenue for CRISPR guide RNA design.
Perspectives
The sequence effects studied in this work were discovered by accident. We were running simulations to check the effect of RNA secondary structure on strand displacement rate, and we found large variation among different sequences. This was initially misattributed to secondary structure, but was later found to be caused by differences in the thermodynamics of DNA-DNA and RNA-DNA base pairing.
Eryk Ratajczyk
University of Oxford
Read the Original
This page is a summary of: Controlling DNA–RNA strand displacement kinetics with base distribution, Proceedings of the National Academy of Sciences, June 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2416988122.
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