New Techniques Make RNA Accessible to Study Variants of Uncertain Significance

By Bio-IT World Staff 

October 3, 2024 | New work from Dr. Lachlan Jolly and the University of Adelaide’s Neurobiology Research Group is using cutting-edge RNA-based techniques to resolve genetic variants of uncertain significance (VUS) that can't be diagnosed through traditional methods. Many disease-causing genes do not express RNA in accessible tissues like blood or skin, leaving many patients without a clear diagnosis. To overcome this, the team is utilizing two innovative methods—transactivation and transdifferentiation. 

Transactivation, based on CRISPR technology, reprograms skin cells to “turn on” any gene, making it possible to obtain RNA from otherwise silent genes. Transdifferentiation, on the other hand, transforms skin cells into other types of cells, such as neurons, where these silent genes are naturally active. This enables researchers to access RNA from disease-causing genes that are typically expressed in tissues like the brain, liver, or heart, which are otherwise inaccessible for diagnostic purposes. 

By applying these techniques, Jolly’s team is able to activate and study over 230 previously silent genes, providing vital RNA data for diagnosing genetic conditions. The success of these methods in activating rare neurodevelopmental genes is a major step toward improving genetic diagnostics and creating new avenues for RNA-based treatments. This work has the potential to help millions of people with undiagnosed genetic conditions by providing the RNA evidence needed for diagnosis. For more on how these technologies are changing genetic research, read the full article at Diagnostics World News.