Shortening GAA repeats in Friedreich’s Ataxia

Repetitive DNA sequence expansions cause over 50 neurological diseases, such as ALS, Huntington’s Disease, Fragile X syndrome and Friedreich Ataxia. The severity of these diseases often correlates with the length of the repeated DNA sequence, suggesting that reducing the length of these repeats could be a promising therapeutic approach. Graduate student David Barryman at the University of Florida plans to explore this possibility in FA by testing different strategies to shrink the GAA repeats in the FXN gene. This approach involves using advanced gene-editing tools based on the CRISPR technology, as well as modulating the DNA repair factors that have been shown to contribute to the GAA repeat expansion. The effects of these strategies on the GAA repeat length will be studied in both dividing and non-dividing cells in a dish, and the relationship of repeat length with frataxin protein expression will be determined. These experiments will provide insights into the feasibility of repeat length modulation in FA and whether shortening repeats will also increase frataxin levels. The hope is that understanding the unique characteristics of the repetitive DNA sequence in FA will pave the way to the development of effective therapies.