Development of a Multivalent Gene Therapy to Correct Cryptic Splicing in ALS

RNA binding proteins help cells control how genetic information becomes working proteins, and Gene Yeo, Ph.D., M.B.A., at UC San Diego investigates how their disruption contributes to neurodegenerative disease. Yeo focuses on ALS, a severe motor neuron disease in which the RNA binding protein TDP-43 moves from the nucleus to the cytoplasm, loses normal RNA processing functions, and triggers cryptic exons that damage key neuronal genes, including one linked to motor neuropathy. His group maps these RNA changes and develops small nuclear RNA guides packaged in AAV vectors to block harmful splice sites and restore healthy RNA and protein levels. In cell cultures and a humanized mouse model, this strategy improves axon growth and supports the idea that multiplexed RNA-targeted therapies could correct multiple disease pathways at once. Series: "Stem Cell Channel" [Health and Medicine] [Show ID: 41166]