Ad-CMV-DN-PP2Acα

Ad-CMV-DN-PP2Acα is an experimental recombinant adenovirus-based gene therapy vector designed to inhibit protein phosphatase 2A (PP2A). It utilizes the constitutive cytomegalovirus (CMV) promoter to drive the expression of a dominant negative mutant form of the PP2A catalytic subunit alpha (DN-PP2Acα), specifically the L199P mutant. By overexpressing this dominant negative subunit, the vector competitively inhibits endogenous PP2A activity, leading to the hyperphosphorylation of PP2A substrates. In preclinical models of hepatocellular carcinoma (HCC), this inhibition results in G2/M phase cell cycle arrest and the induction of apoptosis. While effective against HCC cells, the use of the CMV promoter makes the expression non-specific, causing cytotoxicity in both cancerous and normal liver cells, which led researchers to focus on tissue-specific alternatives like the AFP enhancer/pgk promoter-driven construct.