Scientists have used CRISPR gene editing to target and rapidly destroy glioblastoma cells in an approach that could apply to other highly mutated cancers.
Using a technique they’ve dubbed “cancer shredding,” the researchers at Gladstone Institutes programmed CRISPR to zero-in on repeating DNA sequences present only in recurrent tumour cells – and then obliterate those cells by snipping away at them.
Working with cell lines from a patient whose glioblastoma returned after prior treatments, the team used CRISPR to destroy the tumour cells while sparing healthy cells.
“Glioblastoma is the most common lethal brain cancer, and patients still don’t have any good treatment options,” says Christof Fellmann, who led the study at Gladstone. “Patients typically receive chemotherapy, radiation, and surgery, but most relapse in matter of months. We wanted to find out if we could do something outside the box that could get around this problem of recurrence.”
CRISPR as a therapeutic approach
In glioblastoma, as with many other highly recurrent cancers, tumour cells that escape treatment develop multiple genetic adaptations that allow them to proliferate. The Gladstone team realised that these mutated cells have a unique genetic signature that could be targeted.
“We see CRISPR as a gateway to a new therapeutic approach that won’t be subject to the possibility of tumour cell escape,” Fellmann says. “Cancer shredding could hold potential not only for glioblastoma, but possibly for other hypermutated tumours.”
Much of the work was conducted in the lab of Gladstone Senior Investigator Jennifer Doudna, an author of the paper, who received the 2020 Nobel Prize in Chemistry for her co-discovery of the CRISPR-Cas9 gene editing technology.
UK regulators approved the first CRISPR-based therapy in October 2023, before then, CRISPR was not used as a treatment modality in of itself.
First author I-Li Tan said: “We understand so much today about glioblastoma and its biology, yet the treatment regimens haven’t improved. Now we have a precise way to target the cells that are driving the cancer, and we hope this may one day lead to a cure.”
Image shows: Gladstone Investigator Jennifer Doudna (right) with I-Li Tan (far left), senior author of the study.