4.33 Engineering Viruses For Gene Therapy

Abstract

Gene therapy, the introduction of therapeutic genetic material to cells to ameliorate disease or injury, holds great potential for the treatment of numerous disorders. However, broad clinical application of gene therapy is currently hindered by the need for safer and more efficient delivery vectors. Vectors for gene delivery typically consist of a nucleic acid associated with a material, either natural (e.g., based on viruses) or synthetic (e.g., based on polymers or lipids). While viral vectors offer an attractive platform for gene delivery because of their efficient gene transfer capabilities, their clinical utility is often limited by the natural transduction patterns of viruses and, in many cases, their unfavorable interactions with the immune system. Various approaches have been pursued to address the challenges associated with therapeutic gene delivery, including efforts to tailor the properties of existing viral vectors through rational design and library-based selection (i.e., viral protein engineering), as well as strategies to assemble ‘artificial viruses’ from biological or synthetic building blocks. This chapter discusses current progress toward designing both viral and nonviral gene delivery vectors and describes future directions of the field, including the design of genetic cargo and the integration of gene vectors into biomaterial scaffolds.