AAV-CRISPR-Hdac1-gRNA

AAV-CRISPR-Hdac1-gRNA is an experimental gene therapy designed to modulate the expression of Histone deacetylase 1 (Hdac1) in the brain. Developed by researchers at the University of Maryland School of Medicine, the therapy utilizes a CRISPR interference (CRISPRi) system. In this approach, an adeno-associated virus (AAV) vector delivers a specific guide RNA (gRNA) targeting the Hdac1 gene to D1-type medium spiny neurons (D1-MSNs) in the nucleus accumbens. This gRNA works in conjunction with a catalytically dead Cas9 (dCas9) fused to a Krüppel-associated box (KRAB) repressor domain (SpdCas9-KRAB) to epigenetically silence Hdac1. The primary indication is the treatment of opioid use disorder, specifically to prevent negative affective behaviors and anxiety-like symptoms associated with fentanyl abstinence.