Enhancement of Polymer-Mediated Transgene Expression Using Histone Deacetylase Inhibitors (HDACi)

Polymeric vectors are promising agents for transgene delivery because of their flexibility of structural design, capacities for delivering transgenes in the size of a few hundred nanometers, reduced immunogenicities, and low production costs. However, polymer-mediated gene delivery suffers from low transgene expression levels. Here we demonstrate that chemotherapeutic inhibitors of intracellular histone deacetylases (HDACs) enhance polymer-mediated transgene expression levels in cancer cell lines. Chemotherapeutic inhibitors of both cytoplasmic and nuclear HDACs were investigated for enhancing polymer-mediated transgene expression of reporter proteins (e.g. luciferase). The potential role of nuclear vs. cytoplasmic HDACs, and the HDAC-interacting proteins on enhancing the efficacy of polymer gene delivery was also investigated. Our results demonstrate that inhibiting HDACs can be employed as a synergistic strategy for enhancing polymer-mediated transgene delivery to cancer cells.