Using a gene-editing system originally developed to delete specific genes, MIT researchers have now shown that they can reliably turn on any gene of their choosing in living cells. This new application for the CRISPR/Cas9 gene-editing system should allow scientists to more easily determine the function of individual genes, according to Dr. Feng Zhang, the W.M. Keck Career Development Professor in Biomedical Engineering in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering, and a member of the Broad Institute and MIT’s McGovern Institute for Brain Research. This approach also enables rapid functional screens of the entire genome, allowing scientists to identify genes involved in particular diseases. In a study published online on December 10, 2014 in Nature, Dr. Zhang and colleagues identified several genes that help melanoma cells become resistant to a cancer drug. Silvana Konermann, a graduate student in Dr. Zhang’s lab, and Dr. Mark Brigham, a McGovern Institute postdoc, are the paper’s lead authors. The CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have previously harnessed this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut. In the past two years, scientists have developed Cas9 as a tool for turning genes off or replacing them with a different version. In the new study, Dr. Zhang and colleagues engineered the Cas9 system to turn genes on, rather than knock them out.
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