Gene transfer with modified polyethylenimines

Branched and linear polyethylenimines (PEIs) have proven to be efficient and versatile agents for gene delivery in vitro. In addition, systemic administration of positively charged DNA/PEI complexes results in significant reporter gene expression in lungs. However, re-targeting of complexes to organs other than the lung is hampered by non-specific interactions of polyplexes with blood components and non-target cells. Thus, despite considerable transfectional activity, the properties of PEIs need to be further improved. Therefore, various modifications of PEIs have been explored in recent years. For example, to increase the circulation half-life of the DNA complexes, the surface charge of the particles was shielded by grafting hydrophilic polymers such as polyethylene glycols (PEGs) onto their surface. Alternatively, incorporation of certain ligands into the DNA complexes also resulted in charge shielding even without PEGylation. Herein, I review the most recent PEI derivatives, with a special focus on PEGylated and targeted polymers.