Researchers have used CRISPR-Cas9 to target DNA sequences specific to cancer, shrinking tumors and improving the survival rates of cancer-stricken mice (Credit: vchalup2/Depositphotos)

The CRISPR-Cas9 genome editing system can do some pretty amazing things, giving us new ways to fight muscular dystrophy, blindness, and even HIV. But at the top of its hit list is cancer, and now researchers from the University of Pittsburgh have used the tool to target what they call cancer's command center, in a treatment that's been shown in mice to shrink aggressive tumors and increase survival rates without harming healthy cells.

The technique works by targeting fusion genes, mutations created when two separate genes combine into one hybrid that often leads to cancer. In previous work, the team found that a fusion gene known as MAN2A1-FER was associated with cancer of the prostate, liver, lungs and ovaries, and it helps the tumors grow and spread.

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But the unique DNA fingerprint of fusion genes could be their own undoing. CRISPR-Cas9 is used to target specific DNA sequences and replace them with something else, so delivering the gene editing tool through viruses, the researchers were able to seek out these fusion gene patterns and replace them with cancer-killing genes instead. The other upside is that, unlike conventional treatments like chemotherapy, the new approach will only attack cancer cells, leaving healthy cells undamaged.

In the University of Pittsburgh study, the team transplanted human prostate and liver cancer cells into mice, then treated one group with the CRISPR tool that targets those fusion genes. As a result, the tumors shrunk by up to 30 percent, didn't spread through the body, and the animals all survived to the end of the eight-week test. Meanwhile, in a control group that received the same treatment targeting fusion genes that weren't present in their bodies, the tumors grew almost 40 times larger and in most cases, spread to other parts of the body. None of the control group survived to the end of the test period.

CRISPR-Cas9 has already been put to work in human trials, but these involved editing human immune cells to better fight cancer. The new technique goes over the heads of the "foot soldiers" of the battle and instead targets the "command center" directly.

"This is the first time that gene editing has been used to specifically target cancer fusion genes," says Jian-Hua Luo, lead author of the study. " It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer. Other types of cancer treatments target the foot soldiers of the army. Our approach is to target the command center, so there is no chance for the enemy's soldiers to regroup in the battlefield for a comeback."

While the current work shows that the technique can cause the cancer cells to go into remission, the researchers plan to test whether it could be used to completely wipe it out instead.

The research was published in the journal Nature Biotechnology.

Source: University of Pittsburgh

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CRISPR gene-editing tool targets cancer's "command center" - Gizmag - New Atlas

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