Related Experiment Video
Updated: Aug 12, 2025
11:24
Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
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A universal deep-learning model for zinc finger design enables transcription factor reprogramming
David M Ichikawa1,2, Osama Abdin3, Nader Alerasool4
1Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY, USA.
Nature Biotechnology
|January 26, 2023
Summary
Researchers developed ZFDesign, a deep-learning tool, to engineer Cys2His2 zinc finger (ZF) domains for precise gene regulation. This breakthrough enables custom targeting of any genomic sequence for therapeutic applications.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Cys2His2 zinc finger (ZF) domains are key tools for programmable gene regulation.
- Designing ZFs for specific genomic targets is complex due to intricate DNA-protein interactions.
Purpose of the Study:
- To develop a computational method for designing ZF domains that can bind any specific genomic target sequence.
- To create a versatile platform for gene regulation with potential therapeutic applications.
Main Methods:
- Screening of 49 billion protein-DNA interactions.
- Development of ZFDesign, a deep-learning model utilizing a hierarchical transformer architecture.
- Modeling of global and target-specific differences in ZF-DNA binding.
Main Results:
- Successful design of ZF domains for targeted genomic binding using the ZFDesign model.
- Demonstration of designed ZFs as nucleases, activators, and repressors.
- Seamless reprogramming of human transcription factors using designed ZFs.
Conclusions:
- ZFDesign offers a powerful solution for designing custom ZF domains for any genomic target.
- Designed ZFs can be applied to modulate gene expression for therapeutic purposes, including treating haploinsufficiency and gain-of-function mutations.
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