AAV-DIO-HDAC5-3SA

AAV-DIO-HDAC5-3SA is a viral-mediated gene therapy construct used in preclinical research to investigate the cell-type-specific role of histone deacetylase 5 (HDAC5) in neuropsychiatric disorders, particularly substance use disorders. The construct utilizes an adeno-associated virus (AAV) vector to deliver a Cre-dependent (Double-floxed Inverse Orientation, or DIO) transgene. The transgene encodes a mutant version of HDAC5 known as 3SA, in which three key serine residues (typically S259, S280, and S498) are mutated to alanine. These mutations prevent phosphorylation-dependent nuclear export, resulting in a constitutively nuclear and active form of the enzyme. By deacetylating histones and other nuclear proteins, HDAC5-3SA acts as an epigenetic repressor, suppressing the transcription of genes involved in neuronal excitability and ion transport. In animal models of opioid use disorder, this tool has been shown to limit relapse-associated behaviors by suppressing the firing rates of medium spiny neurons in the nucleus accumbens.

Other names

Cre-dependent AAV-HDAC5-3SAAAV-EF1a-DIO-HDAC5-3SAAAV-EF-1a-DIO-HDAC5-3SAAAV-EF 1a-DIO-HDAC5-3SA