New Method for Turning Genes On and Off Could Enable More Complex Synthetic Biology Circuits

MIT researchers have shown that they can turn genes on or off inside yeast and human cells by controlling when DNA is copied into messenger RNA — an advance that could allow scientists to better understand the function of those genes. The technique could also make it easier to engineer cells that can monitor their environment, produce a drug, or detect disease, says Dr. Timothy Lu, an assistant professor of electrical engineering and computer science and biological engineering and the senior author of a paper describing the new approach that was published online on August 26, 2013 in the journal ACS Synthetic Biology. “I think it’s going to make it a lot easier to build synthetic circuits,” says Dr. Lu, a member of MIT’s Synthetic Biology Center. “It should increase the scale and the speed at which we can build a variety of synthetic circuits in yeast cells and mammalian cells.” The new method is based on a system of viral proteins that has been exploited recently to edit the genomes of bacterial and human cells. The original system, called CRISPR, consists of two components: a protein that binds to and slices DNA, and a short strand of RNA that guides the protein to the right location on the genome. “The CRISPR system is quite powerful in that it can be targeted to different DNA binding regions based on simple recoding of these guide RNAs,” Dr. Lu says. “By simply reprogramming the RNA sequence you can direct this protein to any location you want on the genome or on a synthetic circuit.” Lead author of the paper is Fahim Farzadfard, an MIT graduate student in biology. Samuel Perli, an MIT graduate student in electrical engineering and computer science, is also an author. In previous studies, CRISPR has been used to snip out pieces of a gene to disable it or replace it with a new gene. Dr.
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