A 2-piece gene therapy for difficult-to-treat diseases

In 2023, the US Food and Drug Administration approved the first gene therapy for Duchenne muscular dystrophy (DMD). But that therapy, Elevidys, can’t replace the entire dystrophin gene, the absence of which causes DMD. Instead, it inserts a gene that codes for a smaller version of the dystrophin protein because the whole gene is too big to be replaced by one adeno-associated virus (AAV) vector. But researchers theorize that the closer one can get to replicating the entire gene, the better the therapeutic results will be. Dividing the gene into multiple fragments for delivery by multiple adenovirus vectors could solve the problem. Researchers from the University of Rochester developed a technology they call StitchR that mends two messenger RNA fragments from a split gene together ( Science 2024, DOI: 10.1126/science.adp8179 ). Once the gene fragments are transcribed into mRNA , ribozymes cleave the ends of the mRNA that need to