In parallel to work with ASOs and divalent siRNAs, impressive prion disease survival extension has been reported with recombinant adeno-associated virus (AAV)-delivered gene therapies that either silence the transcription of Prnp alleles in mouse brains with customized Prnp-specific zinc finger repressors (ZFRs) [17,18] or through methylation of Prnp promoter sequences by an epigenetic editor [19]. Here, PRNP is linked to prion disease.