Diagnosing rare genetic diseases presents a significant challenge due to their complex and often hidden nature. These conditions can arise from a diverse array of genetic variations, many of which are uncommon or specific to each individual, complicating the identification of the exact cause of symptoms. Until recently, unraveling these mysteries involved extensive genetic testing and comparing an individual’s genetic profile against established disease patterns. Complicating matters further, many relevant genes are inactive in commonly tested tissues like blood and skin, which makes it difficult to get a clear picture of the genetic basis of these diseases. This complexity not only prolongs the diagnostic process but also extends patient and family uncertainty and delays the initiation of suitable treatments. Now, a new study could mark a significant step forward in the rapid and efficient diagnosis of these complex diseases, which can affect any part of the body.

At Aarhus University in Denmark, researchers have employed CRISPR technology to activate genes in easily accessible cells such as skin or blood. This technique enables the measurement of the correct assembly of messenger RNA - a biological process known as splicing. This advancement is significant since approximately 19% of genes associated with diseases are inactive in readily obtainable tissues like skin and blood cells. Using CRISPR activation, a groundbreaking method that “switches on” normally inactive genes, the researchers successfully activated the MPZ gene, typically active only in the insulating layer of nerve pathways. By activating this gene in skin cells, the team has opened new avenues for analyzing, diagnosing, and understanding genetic diseases.

This innovative approach aims to enhance the efficiency, accuracy, and accessibility of diagnosing genetic diseases. The research team is already working to integrate this technology into clinical diagnostics. This method could significantly contribute to making accurate diagnoses when splicing variants are identified. Furthermore, the team is exploring the wider application of this method and plans to validate a larger panel of genes to determine how the technique can be expanded and modified for even simpler clinical applications.

"With CRISPR activation, the gene can be turned on in a natural environment. There's no need for gene modification in cell models; one can simply take a sample from the patient," said Uffe Birk Jensen from Aarhus University. “The same method can be used for different patients and easily adapted to other genes, and the advantage is that it's very fast with the possibility of results within a few weeks.”