Common Medications May Affect CRISPR Therapy and Cancer Precision Treatment Outcomes

In a new study, scientists from the Max Planck Institute for Evolutionary Anthropology analyzed the effects of over 2,000 clinically approved drugs on DNA repair and CRISPR genome editing outcomes. They discovered compounds that could be used to improve genome editing, molecules that can selectively kill cultured cancer cells, and further identified two proteins with novel functions in DNA repair.

How DNA Repair Affects Genome Editing

DNA double-strand breaks are critical damages in the genome that can be repaired through various pathways. Some repair processes are rapid but introduce additional mutations at the damage site, while others take longer but allow for precise correction. In genome editing, these pathways can be utilized to introduce mutations into human cells. This involves using programmable CRISPR-Cas gene scissors to cut DNA at specific locations in the genome. The resulting breaks must be repaired by the cell for survival, and researchers can provide DNA templates carrying desired mutations. The efficiency of integrating these mutations largely depends on the activity of repair pathways, thus requiring tools to suppress competitive pathways to improve the efficiency of achieving desired outcomes.

A team of scientists from the Max Planck Institute for Evolutionary Anthropology investigated how FDA-approved drugs affect the selection of DNA repair pathways. "As these therapies enter real-world clinical use, understanding how everyday medications interact with CRISPR-based treatments will become increasingly important," said Dominik Macak, co-first author of the study published in Nature Communications.

Drug Interactions and New Discoveries

With the first CRISPR gene therapy approved in the United States, United Kingdom, and European Union at the end of 2023, patients receiving such treatments may also be taking common medications for infections or chronic conditions. Some of these routine medications can affect cellular processes like DNA repair, which may in turn impact the effectiveness or safety of the therapies.

Figure 1. Synthetic lethality by drugs repurposed as DSB repair pathway outcome inhibitors. (Macak D, et al., 2025)

The scientists created a comprehensive map showing how clinically approved drugs affect how human cells repair broken DNA. They tested over 7,000 drug conditions to determine how each compound alters the selection of DNA repair following targeted CRISPR cutting. "We anticipate that this catalog will become a valuable resource for clinicians and researchers working in disease modeling, gene therapy, and oncology," added co-first author Philipp Kanis.

The team discovered several drugs capable of influencing major repair pathways. Using the screening data, they further explored previously unrecognized drug targets that had the greatest impact on repair outcomes. Notably, they discovered new roles in DNA repair for two proteins previously unrelated to genome editing: estrogen receptor 2 (ESR2) and aldehyde oxidase 1 (AOX1). Targeted inhibition of ESR2 can increase the efficiency of precise editing by up to fourfold, while drugs inhibiting AOX1 can be used to kill cultured cancer cells that lack one repair pathway-a condition applicable to many cancer cells.

"Our study identified several approved drugs as promising candidates for treating cancers with DNA repair deficiencies, offering potential options beyond current therapies," said Stephan Riesenberg, senior researcher on the project. "However, further research is needed to validate whether our findings from cultured cell experiments can truly translate into real-world medical applications."

Reference

Macak D, et al. Repurposing clinically safe drugs for DNA repair pathway choice in CRISPR genome editing and synthetic lethality. Nature Communications, 2025.