AAV-CRISPR-KRAB-MeCP2(TRD)

AAV-CRISPR-KRAB-MeCP2(TRD) is an experimental gene therapy platform designed for allele-specific epigenome editing to treat late-onset Alzheimer's disease (AD). Developed by researchers at Duke University and optioned to CLAIRIgene, the system utilizes an adeno-associated virus (AAV) vector to deliver a compact CRISPR-based transcriptional repressor. The active component is a fusion protein comprising a deactivated Staphylococcus aureus Cas9 (dSaCas9) linked to two transcriptional repression domains: the Krüppel-associated box (KRAB) and the transcription repression domain (TRD) of MeCP2 (methyl-CpG binding protein 2). By targeting the ε4 allele of the apolipoprotein E (APOE) gene with specific guide RNAs, the platform induces robust and sustainable gene silencing through epigenetic modification rather than DNA cleavage. Preclinical studies in human iPSC-derived neurons and humanized mouse models have demonstrated its ability to specifically knockdown APOE ε4 expression in the central nervous system.

Other names

AAV-CRISPR-nuclease platform