Gene Delivery into Cells and Tissues
There are significant engineering challenges in translating the remarkable medical implications of gene and nucleic acid delivery from cell and animal models into the clinic. Off-target effects and inefficient delivery to the proper intracellular compartment of the targeted cells are major obstacles to success. Systemic delivery of any viral or nonviral vector requires an appreciation of the adverse physiological barriers that exist in vivo and incorporation of well-designed vector components that limit non-specific uptake and accelerated clearance. In addition, the genetic engineer should consider the design criteria related to cell-specific action. For example, cell surface recognition can increase the therapeutic index of a DNA- or RNA-based medication. Finally, one must consider the mechanism of cellular internalization, and investigators should attempt to target pathways and incorporate vector functionalities that will mediate trafficking to the subcellular compartment that is optimal for activity of the nucleic acid cargo. This chapter discusses key aspects of biodistribution and cellular uptake of nanoparticulate vectors and vehicles. It also surveys current strategies for engineering effective viral and nonviral packaging systems, systems for both targeted, systemic delivery and controlled, local release of nucleic acids or genes from engineered scaffolds, and strategies for directing the intracellular trafficking of vehicle contents to the nucleus or cytoplasm of target cells. © 2014 Elsevier Inc. All rights reserved.
