PRNP and hydrops fetalis: Having validated the improved brain penetrance of 9P31 capsids, we next tested if the retro-orbital injection of 9P31-SlugCas9-HF-MM1 can be more efficient in reducing PrPC levels than the approximate 5% PrPC lowering achieved when we injected AAV9-SlugCas9-HF-MM1 intrathalamically (Fig 5).