Scientists have found a way to manipulate gene expression using the gene editing tool CRISPR, and they have shown that it is possible to control one aspect of the inflammatory response this way. This process, which relies on the manipulation of a gene called IL1RN, can change how cells respond to external signals. The researchers suggested that this method could be used to create therapeutics for inflammatory or chronic disorders such as myeloid leukemia. The work has been reported in Science Advances.
The activity of genes has to be carefully controlled; genes must be expressed at the right time and in the right places. Cells have many different ways to control gene activity, one of which is through epigenetics. This refers to changes in the genome that do not alter the sequence, but can change gene expression, and this can include structural changes that make certain parts of the genome accessible or not, or chemical groups that are attached to or removed from DNA, such as methyl groups.
Cancer and other diseases can arise when genes are activated at the wrong time. Some of this aberrant activation may be due to genetic 'switches' that are turned on or off inappropriately, through methylation.
In this study, the researchers aimed to use CRISPR to alter the methylation status of the human IL1RN gene in a cell line. They found that the activity of IL1RN can be precisely controlled with this technique.
The work also showed that the expression of IL1RN influences the creation of inflammatory cells, which respond incorrectly to external signals. The production of these disruptive cells leads to the generation of modified inflammatory cytokines, which can trigger inflammation. In research models, this mechanism also influenced the growth of tumors.
But the work has indicated that it may be possible to reduce tumor growth, inflammatory disease, and aberrant signaling by altering the activity of IL1RN, and possibly other inflammatory genes.
Now that researchers know that it is possible to modulate certain genes to reduce the proliferation of tumors or tamp down inflammation, they can start to develop therapeutic strategies that could be used in the clinic.
More work will be needed before we know this approach is safe and effective in people, but it is an important demonstration that this concept could potentially treat diseases such as myeloid leukemia, and maybe other disorders related to inflammation as well.
Sources: Josep Carreras Leukaemia Research Institute, Science Advances
