Massachusetts Institute of Technology (MIT) researchers have developed a protein-based sensor that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death. The findings appeared in the journal Nature Methods.
"There is a range of applications for which this could be important," said study senior author James Collins, professor at MIT. "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," Collins noted. "The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want," lead author Shimyn Slomovic from MIT noted.
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.
The researchers achieved this by exploiting a type of protein known as an "intein" -- a short protein that can be inserted into a larger protein, splitting it into two pieces. The MIT researchers also deployed this system to kill cells by linking detection of the DNA target to production of an enzyme called NTR. The researchers are now adapting this system to detect latent HIV proviruses, which remain dormant in some infected cells even after treatment.
"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," Slomovic said.
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