Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer. One way to discover the role of these mutations is to breed a strain of mice that carry the genetic flaw — but breeding such mice is an expensive and time-consuming process. Now, MIT researchers have found an alternative. They have shown that a gene-editing system called CRISPR (clustered regularly interspaced short palindromic repeats) can introduce cancer-causing mutations into the livers of adult mice, enabling scientists to screen these mutations much more quickly. In a study appearing in the journal Nature, the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten. They are now working on ways to deliver the necessary CRISPR components to other organs, allowing them to investigate mutations found in other types of cancer.
CRISPR relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this bacterial 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 some cases, the researchers simply snip out part of a gene to disrupt its function; in others, they also introduce a DNA template strand that encodes a new sequence to replace the deleted DNA.
Studies of genetically engineered mice have yielded many important discoveries, but the process, which requires introducing mutations into embryonic stem cells, can take more than a year and costs hundreds of thousands of dollars. Using Cas enzymes targeted to cut snippets of p53 and pten, the researchers were able to disrupt those two genes in about 3% of liver cells, enough to produce liver tumors within three months. Read the article preview.
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