LAY SUMMARY

Can RNA Trans-Splicing Boost Frataxin Levels in Friedreich’s Ataxia?

Drs. Jonathan Gootenberg and Omar Abudayyeh’s project aims to increase frataxin protein levels in FA patients by improving translation of the patient’s own FXN mRNA. Using a protein-free trans-splicing platform called PRECISE, the team will replace exon 1 of FXN mRNA with an engineered version containing an optimized 5’ UTR to enhance translation. This approach is designed to restore frataxin protein output 5–10 fold without introducing a new gene or permanently altering DNA. By maintaining natural regulation of the gene, it avoids the risks associated with overexpression and conventional gene therapy. If successful, this strategy could provide a safe and effective way to compensate for the transcriptional deficits that cause FA, potentially improving mitochondrial function and reducing cell damage in affected tissues.