Angela Lek, Brenda Wong, Allison Keeler, Meghan Blackwood, Kaiyue Ma, Shushu Huang, Katelyn Sylvia, A Rita Batista, Rebecca Artinian, Danielle Kokoski, Shestruma Parajuli, Juan Putra, C Katte Carreon, Hart Lidov, Keryn Woodman, Sander Pajusalu, Janelle M Spinazzola, Thomas Gallagher, Joan LaRovere, Diane Balderson, Lauren Black, Keith Sutton, Richard Horgan, Monkol Lek, Terence Flotte
We treated a 27-year-old patient with Duchenne's muscular dystrophy (DMD) with recombinant adeno-associated virus (rAAV) serotype 9 containing d Sa Cas9 (i.e., "dead" Staphylococcus aureus Cas9, in which the Cas9 nuclease activity has been inactivated) fused to VP64; this transgene was designed to up-regulate cortical dystrophin as a custom CRISPR-transactivator therapy. The dose of rAAV used was 1×1014 vector genomes per kilogram of body weight. Mild cardiac dysfunction and pericardial effusion developed, followed by acute respiratory distress syndrome (ARDS) and cardiac arrest 6 days after transgene treatment; the patient died 2 days later...
September 28, 2023: New England Journal of Medicine