Scientists fix a stubborn gene-editing tool's DNA-opening problem
Zhou Z, Saffarian-Deemyad I, Shi H, Weiss T, Ur-Rehman MM
Crispr
Better versions of small, efficient gene-editing tools like this one could eventually make it faster and cheaper to breed crops with traits like drought tolerance or disease resistance, including in the vegetables you grow at home.
Gene editors work by prying open the two strands of the DNA double helix to find and cut a target sequence, but a tiny natural tool called TnpB is often bad at fully opening that DNA, so it doesn't cut efficiently. Researchers watched the unwinding happen step by step and found it stalls at a halfway-open stage that easily snaps back shut. By changing just three building blocks in the protein, they made it hold the DNA open more reliably, which let it cut better in test tubes and edit genes more successfully when tried in living plants.
Key Findings
DNA unwinding by Ymu1 TnpB proceeds through a discrete, long-lived, partially unwound intermediate before reaching a fully open state
The fully open state forms inefficiently and readily collapses without negative DNA supercoiling
An engineered variant (H4W-L304F-V305R, 'Ymu1-WFR') stabilizes both unwinding states, boosting in vitro DNA cleavage and genome editing in plants
chevron_right Technical Summary
Scientists figured out why a compact gene-editing tool called TnpB often works poorly, then re-engineered it to unwind DNA more reliably, boosting its cutting power and its success rate at editing genes in plants.
Abstract Preview
Original paper
Stepwise DNA-unwinding gates TnpB genome-editing activity.
TnpB is a compact RNA-guided endonuclease and an evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains...
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Crop-improvement refers to the systematic enhancement of plant varieties through selective breeding, genetic modification, and biotechnological approaches to develop cultivars with superior agronomic, nutritional, or environmental traits. This field is essential for addressing global food security,
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