Gene editing to develop new mouse models of lung cancer

Researchers from the Biomedical Innovation and Medical Applications units of the Center for Energy, Environmental and Technological Research (Ciemat), an organization dependent on the Ministry of Science, Innovation and Universities, have developed a new methodology that optimizes the creation of lung cancer models in mice. The study was recently published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Mirentxo Santos and Rodolfo Murillas, CIEMAT researchers who also belong to the oncology section of the Biomedical Research Network Centre (CIBERONC) and the Health Research Institute of the 12th of October Hospital (IIS-H12O), coordinated the work of researchers from the University of Dublin and the Carlos III Health Institute, co-authors of the article, who are also involved.

In particular, the published study developed a new methodology that allows genetic mutations to be introduced into lung tissue and thus study their impact and tumor growth in order to advance the study of lung cancer.

This fact represents an important step forward as it significantly reduces time and cost by accelerating and optimizing the creation of tumor models, demonstrating the effectiveness of this method for the development of new treatments for lung cancer, one of the highest survival rates being reduced by the lack of effective treatments.

Studies that examine and link data from mouse models and human studies offer the best prospects for combating cancer in general and lung cancer in particular. However, traditional modeling technologies are extremely labor-intensive, expensive, and rely on complex selection programs that can take years. This study was conducted in mouse models to establish the involvement of a number of genetic variations in tumor development.

It is worth noting that this study used gene editing tools using CRISPR/Cas9 technology, which allows for precise changes to be made to DNA, to create new lung cancer models that are as close to reality as possible. The research by doctors Santos and Murillas has made it possible to create a more effective lung cancer model thanks to the technology used, which allowed cancer-causing mutations to be introduced directly into adult airway cells, which represents a significant time saving in animal models.

Another novelty in the study was the use of synthetic biomaterials (cationic polymers) to deliver CRISPR/Cas9 reagents into adult lung epithelial cells, which served as nanoparticles carrying the components needed for gene editing directly to the target cells. In addition, the developed methodology has the additional advantage of being used in adult mice of any genetic background (clean, mixed, and even immunodeficient), which can be purchased commercially and without any prior manipulation or genetic modification.

Using gene editing technology, a small cell lung carcinoma model was developed that reproduces the same characteristics of the disease in humans and shows strong similarities to models previously developed using traditional technologies. The study and proof of concept resulted in a gene editing assessment system based on a reporter gene, also called a “tomato reporter.”