Gene-editing technology has successfully targeted cancer’s “command centre”


The CRISPR gene-editing tool has already shown a lot of potential for helping doctors treat the most stubborn diseases, and now scientists have used it to target the “command centre” of cancerous tumours, stopping their growth and boosting survival rates in mice.

In this new study, CRISPR was aimed directly at fusion genes – formed when two genes combine to form a hybrid, resulting in abnormal proteins which often cause cancer or help it to grow.

 

These fusion genes also have a unique DNA fingerprint, which researchers from the University of Pittsburgh were able to use to hunt down and modify them. Specially engineered viruses were then applied to replace the fusion genes with cancer-killing ones.

“This is the first time that gene-editing has been used to specifically target cancer fusion genes,” says lead researcher Jian-Hua Luo. ” It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer.”

CRISPR lets scientists effectively cut and paste the DNA in cells to fix problems or make improvements, and it has already been used to boost immune cells in the fight against certain types of cancers.

In this case, the researchers went for one of the causes of growth, demonstrating a new way to tackle the disease.

A type of fusion gene called MAN2A1-FER was targeted – previously identified by the same team as being present in certain types of aggressive cancer in the prostate, liver, lungs, and ovaries.

“Other types of cancer treatments target the foot soldiers of the army,” explains Luo. “Our approach is to target the command centre, so there is no chance for the enemy’s soldiers to regroup in the battlefield for a comeback.”

 Once modified, the CRISPR-edited, cancer-killing genes were injected into mice carrying human prostate and liver cancer cells. The tumours reduced in size by up to 30 percent, no secondary growths were noted, and all the mice survived until the end of the eight-week test.

In contrast, in a control group of mice that didn’t receive the treatment, the cancer tumours increased nearly 40-fold in size, metastasis or cancer spread was common, and all the animals died before the study ended.

Even better, because fusion genes only occur in cancerous cells, healthy cells are left alone.

This could give the new technique a big advantage over chemotherapy, which has numerous unwanted side effects on healthy parts of the body.

Tackling the fusion genes didn’t kill off the cancer altogether, but there is hope a refined process could make that a possibility for the future.

More research is also needed to see if this can work as well in humans as it does in mice, but as these were human cancers xenografted to mice, the work so far is much more promising than a traditional mouse study.

“[T]he genome approach described here should in principle be applicable to most human cancers carrying fusion genes,” the researchers conclude. paper.

Source:Nature Biotechnology.

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