AI Unlocks “DNA Grammar” for Targeted Gene Editing, Enhancing Gene Therapy, and More

Researchers have used AI to understand patterns in DNA sequences that control when and where genes are active. This work, from The Jackson Laboratory, MIT's Broad Institute, and Yale University, introduces a new tool for precise gene editing. The focus of this study was on DNA regions called cis-regulatory elements (CREs). These are like on-off switches that ensure specific genes are only active in the correct cells. While CREs help direct genes to work in one cell type and not others, the rules—or "grammar"—for how CREs work has been tough to figure out.

To decode these rules, the team analyzed large sets of DNA data using an AI model. This model identified CRE patterns that help activate or suppress genes in particular cells. Researchers then used these insights to design synthetic DNA switches, aimed at specific tissues.

Testing in Living Models

The team tested these synthetic switches, or CREs, in animal models to see how well they worked. They observed successful results, like activating a fluorescent marker only in the liver cells of zebrafish embryos without affecting other tissues. This precise targeting shows the potential for future therapies that would activate genes in just one tissue or organ.

Using this AI approach, scientists created thousands of new CREs, each with unique functions for targeted gene control. This development may lead to genetic treatments for conditions that need specific cell targeting.

Future Uses and Medical Potential

This tool may advance gene editing for research, but it also opens doors for targeted treatments. With the ability to turn genes on or off in precise cell types, scientists see applications in treating genetic conditions or improving tissue repair. As lead researcher Ryan Tewhey noted, this approach could let researchers “fine-tune gene activity in one tissue,” paving the way for treatments with minimal side effects on other cells.

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Further reading: DNA grammar, gene editing, AI in genetics, DNA switches, cis-regulatory elements, targeted gene therapy, cellular precision

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