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Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have developed a method to screen cancer-associated genetic mutations much more easily and quickly than any existing approach. This illustration, by Samuel Gould’s brother Owen Gould, is an artistic interpretation of the research and the idea of “rewriting the genome,” explains Samuel. Illustration Credit: Owen Gould (CC BY-NC-ND 4.0 DEED) |
Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA.
Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily.
The researchers demonstrated their technique by screening cells with more than 1,000 different mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This method, which is easier and faster than any existing approach, and edits the genome rather than introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful than previously thought.
The researchers say this technique could also be applied to many other cancer genes, and could eventually be used for precision medicine, to determine how an individual patient’s tumor will respond to a particular treatment.
“In one experiment, you can generate thousands of genotypes that are seen in cancer patients, and immediately test whether one or more of those genotypes are sensitive or resistant to any type of therapy that you’re interested in using,” says Francisco Sanchez-Rivera, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.
MIT graduate student Samuel Gould is the lead author of the paper, which appears today in Nature Biotechnology.