MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death. This system can be customized to detect any DNA sequence in a mammalian cell and then trigger a desired response, including killing cancer cells or cells infected with a virus, the researchers say. “There is a range of applications for which this could be important,” says Dr. James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). “This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection, with a report system and/or a respond system.” Dr. Collins is the senior author of an article published online on September 21, 2015 in Nature Methods paper describing the technology, which is based on a type of DNA-binding proteins known as zinc fingers. The article is titled “DNA Sense-and-Respond Protein Modules for Mammalian Cells.” These zinc finger proteins can be designed to recognize any DNA sequence. “The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want,” says Dr. Shimyn Slomovic, an IMES postdoc and the paper’s lead author. “This is used in many ways, but not so much for detection. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection.” To create their new system, the researchers needed to link zinc fingers’ DNA-binding capability with a consequence — either turning on a fluorescent protein to reveal that the target DNA is present or generating another type of action inside the cell.
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