Cas9 nickase-mediated contraction of CAG/CTG repeats at multiple disease loci
Alvaro Murillo Bartolome, Alpaugh Melanie, Larin Meghan, Randall Emma, Heraty Laura, Aston Alys N., Rex Durairaj Ruban, Taylor Alysha, Mas Monteys Alejandro, Stöberl Nina, Aeschlimann Pascale, Bhattacharyya Soumyasree, Allen Nicholas D., Puymirat Jack, Davidson Beverly L., Wheeler Vanessa C., Cicchetti Francesca, Lelos Mariah, Dion Vincent · FENS Forum 2024
Expanded CAG/CTG repeats cause at least 15 different neurodegenerative and neuromuscular diseases that all remain without an effective disease modifying treatment. Because the size of the repeat tract accounts for the majority of the variation in disease severity, contracting them presents an attractive therapeutic avenue. Here, we show that the CRISPR-Cas9 nickase targeted to the CAG/CTG repeat itself leads to efficient contractions in Huntington’s disease patient-derived neurons and astrocytes as well as in myotonic dystrophy type 1 patient-derived neurons. Using single-cell DNA sequencing a
ePoster · Neuroscience