Repositioning genes awakens fetal hemoglobin to treat disease. CRISPR editing may change future gene therapy.

Researchers have discovered a promising new approach to gene therapy by reactivating genes that are normally inactive. They achieved this by moving the genes closer to regulatory elements on the DNA known as enhancers. To do so, they used CRISPR-Cas9 technology to cut out the piece of DNA separating the gene from its enhancer. This method could open up new ways to treat genetic diseases. The team demonstrated its potential in treating sickle cell disease and beta-thalassemia, two inherited blood disorders.

In these cases, a malfunctioning gene might be bypassed by reactivating an alternative gene that is usually turned off. This technique, called “delete-to-recruit,” works by altering the distance between genetic elements without introducing new genes or foreign material. The study was conducted by researchers from the Hubrecht Institute (De Laat group), Erasmus MC, and Sanquin, and published in the journal Blood.

Cells depend on the precise reading of DNA sequences to function correctly. This process, known as gene expression, determines which genetic instructions are activated. When this fails, the wrong parts of the genome can be activated, leading to cancers and neurodevelopmental disorders.

Scientists at the University of Geneva (UNIGE) have identified two proteins that play a key role in regulating this essential mechanism, paving the way for promising new treatments that could be more effective and less toxic than those currently available. Their findings are published in Nature Communications.

Human DNA contains over 20,000 genes and would stretch nearly two meters if fully uncoiled. To fit this enormous amount of information into a tiny space within a cell—just 10 to 100 micrometers in diameter—it must be tightly compacted. This is the job of chromatin, a complex of proteins that packages and condenses DNA within the cell nucleus.