Research Alert
Newswise — A team of researchers from Yale School of Medicine (YSM), the Jackson Laboratory, and the Broad Institute of M.I.T. and Harvard has developed a new AI tool capable of designing never-before-seen sequences of synthetic DNA capable of switching on targeted genes in specific cells. The breakthrough could pave the way for improved gene therapies.
Researchers describe the new AI platform, called Computational Optimization of DNA Activity (CODA), in an article published October 23rd in Nature.
The authors say while gene therapies hold the potential to rewrite disease-causing mutations, better methods are needed to deliver the therapy directly to cells that harbor disease, while leaving it inactive in other parts of the body where it could cause harm. The CODA tool creates DNA sequences, called cis-regulatory elements (CREs), which use a complex code to activate genes in specific cells.
“This project essentially asks the question: ‘Can we learn to read and write the code of these regulatory elements?’” said Steven Reilly, PhD, assistant professor of genetics at YSM and one of the senior authors of the study. “If we think about it in terms of language, the grammar and syntax of these elements is poorly understood. And so, we tried to build machine learning methods that could learn a more complex code than we could do on our own.”
The team trained its model on over 775,000 naturally-occurring CREs tested in blood, liver, and brain-related cell types, then tested the novel, AI-generated CREs in the same type of cells. Researchers say in many cases, the synthetic CREs were more specific to a given cell type than natural ones.
“There are a lot of potential solutions out there for lots of different possible things you might want a regulatory element to do,” Reilly said. “Evolution maybe has never wanted to build a really great driver for an Alzheimer’s drug, but that doesn’t mean it can’t exist.”
The paper's first authors were Rodrigo Castro, PhD, of the Jackson Laboratory and Sager Gosai, PhD, of the Broad Institute. The senior authors were Steven Reilly, PhD, of Yale School of Medicine, Pardis Sabeti, PhD, of the Broad Institute, and Ryan Tewhey, PhD, of the Jackson Laboratory.
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