Polymer systems for gene delivery-Past, present, and future

Gene therapy has long sought to treat disease by delivering therapeutic genes to diseased cells. However, its widespread clinical use has faltered in the face of several challenges, most notably in the area of delivery. Efforts to understand the biological barriers that prevent the effective delivery of therapeutic genes to targeted tissues, and developing safe and efficient vectors that can overcome the barriers, stand at the heart of current gene delivery research. The first part of this review provides a comprehensive discussion of the current understanding of these biological barriers and the rich collection of polymers and design strategies that have accumulated from nearly two decades of research aimed at overcoming these hurdles. The second part highlights the challenges that remain and several innovative approaches and methods that have recently been developed representing, in part, the future directions of gene delivery research.