Combination of adenovirus and cross-linked low molecular weight PEI improves efficiencyof gene transduction

Abstract

Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy incancer treatment. However, poor infection efficiency with coxsackievirus and adenovirusreceptor (CAR) down-regulated cancer cell lines is one of the major challenges for itspractical and extensive application. As an alternative method of viral gene delivery, anon-viral carrier using cationic materials could compensate for the limitation ofadenovirus. In our study, adenovectors were complexed with a new synthetic polymerPEI-DEG-bis-NPC (PDN) based on polyethylenimine (PEI), and then the properties of thevehicle were characterized by measurement of size distribution, zeta potential andtransmission electron microscopy (TEM). Enhancement of gene transduction byAd/PDN complexes was observed in both CAR-overexpressing cell lines (A549) andCAR-lacking cell lines (MDCK, CHO, LLC), as a result of facilitating binding and celluptake of adenoviral particles by the cationic component. Ad/PDN complexesalso promoted the inhibition of tumor growth in vivo and prolonged the survivaltime of tumor-bearing mice. These data suggest that a combination of viral andnon-viral gene delivery methods may offer a new approach to successful cancer genetherapy.