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Light-Activated 'CRISPR' Triggers Precision Gene Editing and Super-Fast DNA Repair
by Johns Hopkins University
Very fast CRISPR activated by light [Credit: Ella Marushchenko]
In a series of experiments using human cancer cell lines, scientists at Johns Hopkins Medicine say they have successfully used light as a trigger to make precise cuts in genomic material rapidly, using a molecular scalpel known as CRISPR, and observe how specialized cell proteins repair the exact spot where the gene was cut.
Results of the experiments, published June 11 in Science, not only reveal new details about the DNA repair process, but also are likely, the researchers say, to speed up and aid understanding of the DNA activity that typically causes aging and many cancers.
“Our new system of gene editing allows for targeted DNA cutting within seconds after activation. With previous technologies, gene editing could take much longer — even hours,” says postdoctoral fellow Yang Liu, Ph.D., a member of the Johns Hopkins Medicine research team.
In a time-lapse video over eight hours, a high-powered microscope captures the moment when the CRISPR-Cas9 complex cuts two copies of a gene (red glow in blue circle and purple square) in a living cell. Scale Bar: 5 µm. Credit: Yang Liu, Johns Hopkins Medicine
The powerful CRISPR tool has, in recent years, enabled scientists to easily change, or “edit,” DNA sequences and alter gene functions to speed the pace of research on gene-linked conditions.
Adapted from a naturally occurring gene editing system found in bacteria, CRISPR uses small sequences of genetic material called RNA as a kind of guide that is coded to match and bind to a specific sequence of genomic DNA within a cell. The CRISPR molecule also contains an enzyme called Cas9, which acts as the scalpel to cut out the DNA sequence. Then, the cell uses its own enzymes and proteins to repair the sliced DNA, often adding DNA sequences that scientists slip into the cell.
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Used in dogs with mammary cancer, a model for human breast cancer, the technique was capable of illuminating both the primary tumor as well as lymph nodes where the disease had spread. (Image: Penn Vet)
"Clean margins” are a goal of cancer excision surgery. If even a small piece of cancerous tissue is left behind, it increases the likelihood of a local recurrence and spread of the disease, possibly reducing overall survival time.
With an innovative approach to cancer surgery, researchers at the University of Pennsylvania are investigating a technique to help surgeons clearly see whether they’ve left any diseased tissue behind. Using a dye that glows under near-infrared light and preferentially accumulates in cancer cells, they performed surgery to remove mammary tumors from dogs treated at the School of Veterinary Medicine’s Ryan Hospital.
They found that the technique was able to illuminate not only the tumors but also cancer that had spread to the lymph nodes. Mammary cancer in dogs is akin to human breast cancer in many key ways. The research team believes that, with a different dye that is more specifically targeted to cancer cells, a parallel technique could improve outcomes in breast cancer patients who opt for breast-conserving surgery to treat their disease, The researchers reported this in the journal PLOS ONE.
“Doing this kind of research has two main benefits,” says David Holt, a veterinary surgeon and senior author on the work. “The dogs are a great model for human breast cancer, but there are also some real opportunities to benefit the dogs as well.”