Adenovirus Coating

Top panel: transmission electron microscopy of uncoated and PAMAM coated adenovirus; lower left panel: laser scanning microscopy of epidermal growth factor receptor (EGFR) positive U87MG human glioblastoma cells transduced with PAMAM-PEG-GE11 coated adenovirus (red: EGFR, green: adenovirus, blue: cell nucleus); lower right panel: reporter gene expression (enhanced green fluorescent protein) of EGFR positive A549 human lung carcinoma cells transduced with PAMAM coated adenovirus (top) or EGFR targeted PAMAM-PEG-GE11 coated adenovirus (bottom).

Adenovirus type 5 (Ad) is an efficient gene vector with high gene transduction potential, but its efficiency is dependent on the presence of the Coxsackie- and Adenovirus Receptor (CAR). To enable transduction of CAR negative cancer cell lines, cationic PAMAM dendrimers are attached non-covalently to the capsid. Specificity for tumour cell infection is obtained by retargeting the coated Ad to receptors frequently overexpressed on tumor cells, like EGFR. PAMAM coating enables successful transduction of cells in vitro even in the presence of neutralizing antibodies. In vivo, systemic administration shows de-targeting from the liver and re-targeting to tumor xenografts.