Gene therapy has emerged as one of the most promising avenues for treating hereditary diseases. While there have been significant advances in this field, several challenges, particularly related to gene delivery, still need to be overcome. A key carrier in gene therapy is the adeno-associated viral vector (AAV), known for its efficient gene transfer. However, it has limitations in terms of carrying larger genes reliably. Researchers at the University of Zurich have introduced a new method called REVeRT (reconstitution via mRNA trans-splicing) that could address this limitation and significantly improve gene therapy efficiency. REVeRT is described in a recent Nature Communications paper.
The REVeRT method builds upon the use of dual AAV vectors, which has been a strategy in the past to deliver split genes that can reassemble in the target tissue. What sets REVeRT apart is that it assembles split gene fragments at the transcript level, offering increased efficiency, fewer side effects, and enhanced flexibility. This means larger genes can be divided into fragments at various points.
The researchers have tested and successfully evaluated this method in animal models, especially for treating hereditary macular degeneration with gene therapy. REVeRT's applications extend beyond ophthalmologic use, holding potential in gene therapies for other hereditary or acquired diseases, including blood disorders, age-related conditions, and even gene therapy studies using CRISPR/Cas genome editing.