A South Korean research team from UNIST and the Institute for Basic Science (IBS) has developed a promising innovation in gene editing that brings oncological care one step closer to safer and more effective personalisation. The new method makes it possible to selectively destroy cancer cells via single-strand DNA breaks, using significantly fewer guide RNAs than previously required. This not only reduces the complexity of the treatment, but also minimises the risk of damage to healthy tissue.
The technology builds on CRISPR, but now switches from causing double-strand breaks (DSBs) to single-strand breaks (SSBs). By combining these SSBs with PARP inhibitors, drugs that block the natural DNA repair mechanism, tumour DNA is effectively damaged without the aggressive side effects of previous methods.
The new approach requires only four guide RNAs, a significant reduction from the previous 20+ RNAs. This lowers the threshold for clinical application while maintaining high precision. ‘We are reducing technical complexity and increasing safety, which opens up new perspectives for personalised gene therapy in cancer,’ said Prof. Seung Woo Cho of UNIST.
Broader applicability
Until now, PARP inhibitors have been particularly effective in BRCA-mutated breast cancer and ovarian cancer. Thanks to this new CRISPR combination, other forms of cancer – without specific genetic abnormalities – can also be treated in a targeted manner. This significantly increases the applicability of these therapies.
In preclinical studies, including organoid models of patients with colorectal cancer and mouse trials, the approach showed promising results. Within six weeks, tumour growth was reduced by more than 50%.
Potential for combination therapy with radiotherapy
The researchers also see synergistic opportunities with existing treatments, such as radiation. By suppressing DNA repair mechanisms in cancer cells, this technology could enable lower radiation doses – maintaining effectiveness but with fewer side effects for the patient.
This innovative strategy underscores the power of personalised medicine and the role of digital biotechnology in improving treatment outcomes. By intervening more efficiently and safely at the DNA level, oncological care can be made more targeted, less burdensome and more effective.
The results have been published in Cancer Research and offer a concrete perspective on the next generation of cancer therapies.
