Polymer gene delivery: overcoming the obstacles

• Minor modifications to polymer structure determine transfection properties.
• Efficient gene delivery requires timely release of DNA.
• Serum stability is influenced by charge density and packaging efficiency.
• Cellular uptake pathway is polymer and cell type dependant.

Recent progress in gene therapy has opened doors for the development of new and multifunctional delivery agents based on the tailored synthesis of polymers. These polymers are in their infancy compared with viral agents, which have been optimised during millions of years of evolution, making viral vectors naturally efficient transfection agents. To improve the efficiency of polymer gene delivery to the level seen in viral vectors, it is necessary to understand the challenges faced by polymer gene delivery vectors both in vitro and in vivo. In this review, we analyse and discuss those obstacles that scientists have to overcome to design a highly efficient synthetic transfection agent.