ABSTRACT
This chapter addresses the design of new nanotechnological platforms and the physicochemical properties that make them effective in mediating nucleic acid-based therapies, by overcoming biological impediments. It provides an integrated view of how nonviral delivery systems, differing in their chemical nature and properties, can be modulated in order to improve their ability to carry and deliver nucleic acids to target cells. The chapter explores the strategies displayed by viruses, which have naturally evolved the capacity to elude the obstacles presented by their host organisms. The discovery of other nucleic acids also contributed to the development of new approaches to gene therapy application. The extraordinary complexity of living organisms presents a plethora of challenges to the delivery of nucleic acids to target cells, including the challenges of transposing systemic barriers, such as immune system activation, achieving specific cell targeting, and overcoming cellular barriers. The cellular barriers include the cytoplasmic membrane and intracellular degradation pathways.
