Physical adsorption of PEG grafted and blocked poly-l-lysine copolymers on adenovirus surface for enhanced gene transduction

Polyethylene glycol (PEG) has been chemically immobilized onto the surface of adenoviruses (ADVs) to reduce non-specific immune response and extend blood circulation time while maintaining the high transduction efficiency of a foreign gene into cells. In this study, ADVs encoding an exogenous green fluorescent protein (GFP) were physically coated with PEG grafted and blocked poly-l-lysine (PLL-g-PEG and PLL-b-PEG) copolymers via ionic interactions to comparatively evaluate their gene transduction efficiency. The surface immobilization of ADVs with the two types of PLL–PEG copolymers exhibited significantly increased GFP transduction activity, compared to that of naked ADVs. ADVs coated with PLL-b-PEG showed higher extent of GFP expression than those with PLL-g-PEG under serum conditions. For PLL-g-PEG copolymers, the substitution degree of PEG in the PLL backbone greatly influenced the gene expression level. Additionally, ADVs modified with PLL-b-PEG exhibited greater transduction efficiency for bone marrow derived human mesenchymal stem cells compared to naked or PLL coated ADVs in the serum condition. This study suggests that enhanced ADV gene transduction efficiency can be attained for various cells by simply coating PLL-b-PEG on the surface.

Graphical abstractADVs surface coated with PEG blocked and grafted poly-l-lysine (PLL-b-PEG and PLL-g-PEG) copolymers via ionic interactions showed far superior gene transduction efficiency for cancer cell lines and primary human mesenchymal stem cells compared to naked ADVs.Figure optionsDownload full-size imageDownload as PowerPoint slide