Killing Cancer Cells with Fewer DNA Cuts!... UNIST and IBS Develop Gene-Editing Cancer Therapy

Gene-Editing Scissors and PARP Inhibitors
Enable Selective Cancer Cell Death
Effective Even with Single-Strand DNA Cuts
Reduced Side Effects and Broader Clinical Potential

A new gene-editing cancer therapy that selectively cuts and kills only cancer cell DNA has been developed.

The research team from the Department of Biomedical Engineering at Ulsan National Institute of Science and Technology (UNIST) and the Center for Genomic Integrity at the Institute for Basic Science (IBS) announced on September 3 that they have developed a gene-editing cancer therapy capable of killing cells by cutting just one strand of the double helix in cancer cell DNA.

This gene-editing cancer therapy uses CRISPR scissors to cut out mutations accumulated in cancer cell DNA, thereby selectively killing only cancer cells.

The research team first introduced this technology in 2022, but at that time, more than 20 gene-editing scissors had to be delivered simultaneously to break the double-stranded DNA in order to inflict fatal damage to cancer cells. The delivery of so many scissors was challenging, and there was a high risk of damaging healthy tissue as well.

Research team, (from left) Professor Seungwoo Cho, Professor Jinmyung Joo, Professor Taeun Park, Researcher Soyoung Lee, Researcher Kyunghwan Kim, Researcher Hyejin Jung. Provided by Ulsan National Institute of Science and Technology (UNIST)

The newly developed technique is effective even when only one strand of the DNA double helix is cut. It also requires just four gene-editing scissors. This is possible because the researchers used a strategy that combines the gene-editing scissors with a PARP protein inhibitor. PARP is a protein that repairs single-strand breaks; if PARP does not function properly, single-strand breaks evolve into double-strand breaks.

PARP inhibitors are targeted cancer drugs with fewer side effects, but they are effective only in ovarian and breast cancer patients with BRCA gene mutations. By combining gene-editing scissors with PARP inhibitors, this approach enables the use of PARP inhibitors to kill cancer types that do not have these mutations.

Professor Seungwoo Cho, the corresponding author from the Department of Biomedical Engineering at UNIST, explained, "This research significantly reduces the complexity of the delivery process and cell toxicity, increasing the potential for clinical application. It also expands the scope of targeted cancer therapies using PARP inhibitors."

When the gene-editing scissors and PARP inhibitors were administered to organoid tissue made from the cancer cells of colorectal cancer patients, growth was suppressed. In preclinical experiments where colorectal cancer cells were transplanted into mice, tumor size was reduced to less than half over six weeks.

This technology can also be used to enhance the effectiveness and reduce the side effects of existing radiation cancer therapies. Radiation damages not only cancer cell DNA but also the DNA of healthy cells. However, when combined with gene-editing therapy, even low-dose radiation-which is not very effective on its own-was able to effectively kill cancer cells.

The research team stated, "We expect that this approach will lead to synergistic effects when combined with other targeted cancer drugs or radiation therapy, making it a promising strategy for both standalone and combination therapies."

Gene-editing cancer therapy that cuts mutations found only in cancer cell DNA to kill cancer cells.

The results of this study were published on August 1 in the official journal of the American Association for Cancer Research (AACR), Cancer Research.