CRISPR-mediated DNA methylation editing regulates inflammation and tumor growth

Genes, fragments of DNA located on our chromosomes, control much of what happens in cells. Each cell activates only the genes it needs, silencing the rest through molecular "switches" present on each gene. However, these switches can sometimes be erroneously activated, leading the cell to behave abnormally and potentially resulting in diseases such as cancer or autoimmune disorders.

The activity of these "switches" is regulated by their methylation status, chemical marks that can be added to or removed from DNA. Thanks to new tools based on CRISPR-Cas9 technology, the team led by Dr José Luis Sardina, group leader at the Josep Carreras Institute, has succeeded in controlling the "switch" of the IL1RN gene in cells derived from human leukemia, turning it on or off by adding or removing these chemical marks.

The results of the study, led by Dr Gemma Valcárcel and conducted in collaboration with Dr. Esteban Ballestar's team, have just been published in the prestigious journal Science Advances. The research demonstrates how precise control of IL1RN gene activity affects the production of inflammatory cells that respond abnormally to external stimuli. This altered response causes the cells to produce modified inflammatory cytokines, showing a distinct capacity to modulate tumor growth in laboratory models.

This proof of concept demonstrates that it is possible to regulate the activity of key immune system genes such as IL1RN through DNA methylation, thereby modulating functions like inflammation or tumor progression. Although researchers already suspected that such chemical modifications could influence immune system behavior, this study provides the first experimental evidence confirming that connection and revealing its functional consequences.

With this knowledge and the technological capability to activate or deactivate individual genes with precision, the door is opened to the development of new strategies aimed at intervening in the most fundamental biological processes of immune cells and, potentially, new therapies for certain subtypes of leukemia and other diseases with an inflammatory component.

This work was funded by the Government of Spain, the Government of Catalonia, the Carlos III Health Institute, and Worldwide Cancer Research.