New Cancer Gene Therapy Targets Single-Strand DNA Breaks

Researchers 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) have announced a significant advancement in cancer gene therapy. Their innovative method, published in the journal Cancer Research, allows for the precise destruction of cancer cells by targeting a single strand of their DNA, a safer and more efficient approach than previous methods.

Overcoming Previous Limitations

The new technique builds on the team’s previous CRISPR-based approach from 2022, which required the simultaneous delivery of more than 20 guide RNAs to induce multiple double-strand breaks (DSBs) in cancer DNA, effectively killing the cells. However, this method was complex to deliver and carried a risk of damaging healthy tissues.

The new strategy dramatically simplifies the process by needing only four guide RNAs. It works by creating single-strand breaks (SSBs) in the cancer DNA and then using PARP inhibitors, a class of drugs that block DNA repair proteins, to prevent the breaks from being fixed. This synergistic combination triggers cancer cell death with fewer off-target effects, enhancing safety and making it a more viable candidate for clinical applications.

Expanding the Use of PARP Inhibitors

Historically, PARP inhibitors have been used as targeted therapies primarily for ovarian and breast cancers with specific BRCA mutations. This new gene therapy broadens the potential application of these drugs to other cancer types that lack these genetic alterations. As Professor Seung Woo Cho, the lead corresponding author from UNIST, explained, this advancement “extends the potential use of PARP inhibitors beyond current indications.” The effectiveness of this combined approach was demonstrated in both patient-derived colorectal cancer organoids and in vivo tumor models. In mouse experiments, the therapy was able to reduce tumor growth by over 50% within a six-week period.

Potential for Combination Therapies

The researchers also believe this strategy holds great promise when combined with existing treatments, such as radiation therapy. Since radiation can damage both cancerous and healthy DNA, this new method could allow for the use of lower radiation doses while maintaining therapeutic efficacy, thereby reducing the side effects commonly associated with this treatment. The team anticipates that this method could create synergistic effects when used alongside other targeted therapies, opening up new avenues for personalized and combination cancer treatments.