anti-Aldh2 antisense adenoviral vector

An **anti-Aldh2 antisense adenoviral vector** is an experimental gene therapy construct designed to reduce the expression of the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) in vivo. The vector is an adenovirus encoding an antisense RNA against ALDH2 mRNA, and sometimes co-expresses a fast alcohol dehydrogenase (ADH). The antisense RNA binds to endogenous Aldh2 mRNA, leading to decreased ALDH2 protein synthesis in liver cells via mRNA degradation or translation arrest, thereby reducing its enzymatic activity. The primary mechanism of this therapy is to artificially mimic the naturally occurring "ALDH2*2" phenotype seen in some East Asian populations, which is protective against alcoholism because it results in accumulation of acetaldehyde (a toxic ethanol metabolite) after drinking alcohol, causing aversive reactions and thus reducing alcohol intake. Studies in rats have shown that administration of this vector results in decreased liver ALDH2 activity, increased blood acetaldehyde after ethanol exposure, and a marked reduction in voluntary alcohol consumption. This therapy is being studied as a potential intervention for alcoholism, but it is not approved for clinical use[1][3][4][8].

Other names

AdV-ADH/asALDH2