Reading eighteen letters of DNA
A designed protein that recognises one eighteen-letter stretch of DNA, and the measurements that show how tightly it holds.
Code
ZF-17
Year
2025
Status
Published
Modality
Protein design · fluorescence assays
Funding
Institute core funding
Team
Rana Okafor, Sten Lindqvist, Ilse Maraval
Metric
4 nM
Measured
binding affinity
The question
How specific can a designed DNA-binding protein be? We wanted a protein that holds one sequence far more tightly than anything close to it.
What we built
ZF-17 is a six-finger protein. We generated 1,152 candidates on a computer, screened them on twelve plates, and characterised the best three in detail.
What we measured
The best design binds its target at 4 nM, about forty times more tightly than the natural protein it came from, and drops off sharply when we change a single letter.
What’s next
We are testing how the same design behaves when the DNA is wrapped around a nucleosome instead of free in solution.
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