Innovative Gene Editing Technique Targets Cancer DNA with Precision

Researchers have made significant strides in cancer gene therapy with a new gene editing technology that allows for the selective destruction of cancer cell DNA. This groundbreaking method, developed by experts from the Department of Biomedical Engineering at the Ulsan National Institute of Science and Technology (UNIST) and the Center for Genomic Integrity at the Institute for Basic Science (IBS), simplifies the process of targeting cancer cells by focusing on a single strand of the DNA double helix.

In previous research conducted in 2022, the team utilized a CRISPR-based approach that required the delivery of over 20 guide RNAs to induce multiple double-strand breaks (DSBs) in cancer DNA, leading to cell death. However, this method posed challenges related to the complexity of delivery and the risk of unintentional damage to healthy tissues.

The newly developed technique enhances efficiency by utilizing just four guide RNAs. It takes advantage of the synergy between CRISPR technology and PARP inhibitors, which are drugs that obstruct a vital DNA repair protein. By inducing single-strand breaks (SSBs) rather than DSBs and preventing their repair, this method effectively leads to the death of cancer cells while reducing the risk of off-target effects and enhancing overall safety.

PARP inhibitors are currently recognized as targeted therapies, particularly for ovarian and breast cancers associated with BRCA mutations. The introduction of this combined strategy expands their potential application to various other cancer types that do not exhibit such genetic alterations.

According to Professor Seung Woo Cho from UNIST, this advancement simplifies gene delivery and minimizes cellular toxicity, which could facilitate future clinical applications. This new approach also extends the potential use of PARP inhibitors beyond their existing indications.

The findings from this study, which have been published in the journal Cancer Research, demonstrate the efficacy of this method in patient-derived organoids from colorectal cancer as well as in in vivo tumor models. In experiments conducted on mice, tumor growth was observed to decline by more than 50% within a six-week timeframe.

Furthermore, this innovative strategy holds promise in enhancing the effectiveness of existing radiation therapies. Since radiation tends to damage both cancerous and normal DNA, integrating targeted gene editing with radiation could enable the use of lower radiation doses, thereby reducing adverse side effects while preserving therapeutic effectiveness.

The researchers believe that when combined with other targeted therapies or radiation treatment, this method could produce synergistic effects, paving the way for new avenues in personalized cancer treatment and combination therapies.