An international team of scientists has shown for the first time that CRISPR genome editing technology can be used as a tool to find new gene therapies for lung cancer.
The team led by Associate Professor Rory Johnson, from UCD’s School of Biology and Environmental Sciences and a member of UCD’s Conway Institute, published the findings of the study in the current issue of the scientific journal Cell Genomics .
Lung cancer is the leading cause of cancer mortality. The work aimed to create new avenues for developing non-small cell lung cancer therapies based on RNA therapeutics (RNATX). Recently, RNATX has emerged as a promising new strategy for developing therapies against common diseases.
RNA is part of the genetic information of all living cells. While DNA contains the blueprint instructions, RNA is able to transmit this information and independently perform important biological functions in the cell.
Scientists are particularly interested in “long non-coding RNAs” (lncRNAs), a large but enigmatic class of RNAs discovered in the past decade that have emerged as critical disease genes. This study focused on discovering lncRNA targets in non-small cell lung cancer (NSCLC).
Commenting on the research, Associate Professor Rory Johnson said: “RNATX offers a way to target virtually any disease gene, safely and effectively, while speeding up and saving the drug development process. The biggest hurdle is identifying optimal genetic targets for RNATX in a This project achieves this by combining CRISPR genome editing with lncRNAs to select the most promising lncRNA targets for therapy.”
CRISPR genome editing is a powerful tool that gives scientists a cheap and easy way to find and alter a specific piece of DNA within a cell—the “cut and paste” of the biological world.
Using the CRISPR tool, the team initially identified 80 possible lncRNA targets that are active in NSCLC. Further screening focused on two potential drug targets that have been named Cancer Hallmarks in Lung LncRNA (CHiLL) 1 and GCAWKR. These targets will now be investigated further.
Lung cancer is a critical unmet medical need. It is the biggest cancer killer in Ireland and worldwide. Current therapies do not effectively treat the majority of patients, leading to a poor 5-year survival that has improved little in recent decades.
These findings provide a broadly applicable strategy for discovering new targets for RNATX in virtually any cancer. I want to congratulate Rory and his colleagues around the world on this work.”
Professor Helen Roche, Director of the Conway Institute at UCD
The team plans to further develop the candidate gene targets for preclinical testing with the goal of moving to clinical trials if successful. They will also seek to further improve screening techniques to discover better targets, more quickly and cheaply, and in other types of cancer.
The study was initiated by the Johnson group while at the University of Bern and completed at the University of Dublin, funded by a Science Foundation Ireland (SFI) Future Research Leaders grant to Associate Professor Rory Johnson. The collaborative study also included scientists from research institutions in Spain, Switzerland, Italy, the US, Hong Kong and China.
Source:
UCD Research and Innovation
Journal reference:
Esposito, R., et al. (2022) Multimarker, long non-coding RNA maps reveal non-small cell lung cancer vulnerabilities. Cellular genomics. doi.org/10.1016/j.xgen.2022.100171.