Innovative Gene Editing Technique Targets Cancer DNA with Fewer Guides

Researchers from Ulsan National Institute of Science and Technology (UNIST) and the Center for Genomic Integrity at the Institute for Basic Science (IBS) have introduced a groundbreaking gene therapy approach for cancer treatment. This new method allows for the precise destruction of cancer cell DNA by targeting only a single strand of the DNA double helix, significantly simplifying the process and potentially reducing side effects associated with traditional techniques.

Previously, in 2022, the team developed a CRISPR-based method that involved delivering over 20 guide RNAs simultaneously to induce multiple double-strand breaks (DSBs) in cancer DNA, effectively killing tumor cells. Despite its effectiveness, this approach faced challenges related to delivery complexity and the risk of damaging normal tissues.

The latest innovation reduces the number of guide RNAs required to just four. It exploits the synergy between CRISPR technology and PARP inhibitors—drugs that inhibit a key DNA repair protein. Instead of causing double-strand breaks, this approach induces single-strand breaks (SSBs) and prevents their repair, which selectively triggers cancer cell death while minimizing harm to healthy cells.

PARP inhibitors are already established in targeted therapy for ovarian and breast cancers with BRCA gene mutations. The new method broadens their application to other types of cancers lacking these specific mutations. Professor Seung Woo Cho from UNIST explained that this advancement reduces the complexity of gene delivery and cellular toxicity, which could facilitate clinical translation. He also highlighted that this strategy might expand the use of PARP inhibitors beyond current cancer indications.

The method has demonstrated promising results in patient-derived organoids from colorectal cancer and in vivo tumor models. In mouse experiments, tumor growth was reduced by over 50% within six weeks. Additionally, this strategy shows potential when combined with radiation therapy, as it could enable lower radiation doses, leading to fewer side effects while maintaining therapeutic efficacy. The researchers anticipate that combining this approach with other targeted therapies could produce synergistic effects, paving the way for personalized and combination cancer treatments.

For further details, see the study published in Cancer Research (2025): link.