DNA switches can turn genes on and off very precisely, even in specific organs

An international research team, including scientists from The Jackson Laboratory, the Broad Institute and Yale University, publish their findings in the scientific jour ir method makes it possible to switch on genes only where they are ne – for example, only in the liver or only in the brain. “What’s special about these synthetically design elements is that they are remarkably specific to the target cell type they are design for,” said Ryan Tewhey, co-author of the study. “This gives us the opportunity to increase or decrease the expression of a gene in just one tissue without affecting the rest of the body.”

‘Language’ of genetic switches 

But how does it all work?aturally contains thousands of switches, known as cis-regulatory elements (CREs). These ensure that certain genes are only active when and where they are ne. Until now, however, it has been a whatsapp lead mystery how exactly these switches work – a bit like trying to understand a language without a dictionary. “This has limit our ability to design gene therapies that only affect certain cell types in the human body,” says co-author Rodrigo Castro. The researchers us deep learning, a form of AI, to unravel the ‘language’ of CREs. They f hundrs of thousands of DNA sequences into the system and let the AI ​​analyse how these switches work in different cell types.

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AI Can Create Artificial CREs

After the AI ​​studi the CREs, the researchers next develop CODA (Computational Optimization of DNA Activity), a platform Armat amb els coneixements adequats that can design entirely new DNA switches. To the scientists’ surprise, the artificial switches work even better than their natural counterparts. Not only were they very precise in turning on genes in specific tissues, but they also actively kept genes turn awb directory off in other tissues. To test the effectiveness, the researchers first us cultur cells, and later zebrafish. In the latter, they introduc, among other things, an artificial switch that was suppos to activate a fluorescent protein in the liver. The result was spectacular: only the liver lit up, while the rest of the fish remain dark.

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