CRISPR-based APP-editing therapeutic

CRISPR-based APP-editing therapeutic is an investigational gene therapy being developed by the University of California, San Diego (UCSD) and its spinout startup CRISPRAlz for the treatment of Alzheimer's disease. The therapeutic utilizes a CRISPR-Cas9 system, typically delivered via an adeno-associated virus (AAV) vector, to target and edit the last exon of the amyloid precursor protein (APP) gene. Specifically, it deletes the endocytic YENPTY motif at the C-terminus of APP. This modification prevents the internalization of APP into endosomes where it would normally be cleaved by beta-secretase (BACE1) to produce toxic amyloid-beta (Aβ) peptides and beta-carboxyl-terminal fragments (β-CTF). Instead, the edited APP remains on the cell surface, promoting neuroprotective alpha-secretase cleavage. In preclinical models, this approach has demonstrated robust reductions in amyloid plaque deposition, neuroinflammation, and lysosomal dysfunction, alongside improvements in cognitive and synaptic function.

Other names

AAV-CRISPR-APPCRISPR-based APP-editing approachCRISPR-based APP-editing therapyCRISPR-based amyloid precursor protein (APP)-editing approach