Researchers have discovered a new approach to cancer treatment by combining the benefits of gene editing and a well-known chemotherapy drug. Cancer cells have long been resistant to traditional therapies such as chemotherapy, gene therapy, and immunotherapy. However, this innovative therapy shows promise in improving patient outcomes.
The chemotherapy drug Olaparib is known to shrink tumors by killing cancer cells. However, the success of Olaparib is often impeded by surrounding cells that promote tumor growth. Additionally, chemotherapy is known for its indiscriminate killing of healthy cells, leading to severe side effects.
Gene editing using the CRISPR/Cas9 system offers a personalized and targeted approach to cancer therapy, minimizing off-target effects. The CRISPR/Cas9 system functions as molecular scissors, cutting into a cell’s genetic information and allowing researchers to alter specific sections of genetic material. This approach has been particularly useful in cancers with a genetic basis, such as certain types of breast cancer caused by BRCA gene mutations.
Although gene editing therapy presents opportunities for improving cancer treatment, cancer cells are complex and influenced by various factors. Researchers sought to combine gene editing with chemotherapy to harness the benefits of both approaches.
A recent study published in Advanced Science describes a strategy to inhibit breast cancer tumors by linking CRISPR/Cas9 to the chemotherapy drug Olaparib. To overcome challenges in combining these treatments, researchers used nanocomplexes, which are nano-sized complexes composed of multiple biological molecules. These nanocomplexes effectively delivered the CRISPR/Cas9 machinery and Olaparib to cancer cells.
The resulting therapy, named “combinatorial and bioorthogonal nano-editing complex” or ComBiNE, showed promising results in mouse models. Injecting ComBiNE into tumors reduced tumor growth by 70% compared to untreated tumors. Furthermore, ComBiNE demonstrated specificity for breast cancer cells with BRCA mutations, minimizing side effects on normal cells.
The focus now is on optimizing ComBiNE for clinical application, with further improvements in technology to enable systemic delivery. ComBiNE has the potential to be a versatile tool in biopharmaceutical development, offering a new and exciting approach to treating cancer and other human diseases.
Source: Hee-Sung Park, Hyun Jung Chung, et al., Bioorthogonal CRISPR/Cas9-Drug Conjugate: A Combinatorial Nanomedicine Platform, Advanced Science (2023). DOI: 10.1002/advs.202302253