Designing Polymer-Based DNA Carriers for Non-Viral Gene Delivery: Have We Reached an Upper Performance Limit?

Abstract

Publisher Summary This chapter reviews recent progress for building high-performance polymer-based gene carriers and how to overcome limitations of such carriers. The development of efficient DNA carriers (gene delivery) is one of the key components of gene therapy. The carriers for gene delivery can be divided into two main families: viral carriers and nonviral carriers. Nonviral gene vectors based on synthetic polyamines allow intracellular delivery of genetic material (transfection process). First major limitation is the cellular uptake of the polyplexes. Moreover, assuming that a polyplex can survive endocytosis and successfully escape endosomes, the released material should also survive to the nucleases present in the cytosol before reaching its ultimate target in the cell nucleus. One strategy for controlling the morphology (size, shape, and polydispersity) of polymeric gene carriers is to build the polyplexes on preformed defined nanoparticles. Polymer-based gene vectors can also be constructed on inorganic cores. However, for improving the limitations of polymer-based gene vectors, both the molecular structure and the nanostructure of the polymeric vectors should be adapted to the biological problems encountered either in vitro or in vivo . Abstract The present chapter reports the point of view of a polymer scientist in the field of non-viral gene delivery. Hence, the material science aspects of this therapeutic field are primarily discussed herein. In particular, this chapter reviews recent progress for building high-performance polymer-based gene carriers. The fundamental relation between the structure of these polymeric vectors and their performances in vitro or in vivo is presented. This state-of-the-art review illustrates that the strong limitations of polymeric gene carriers can be potentially overcome if a careful design is made at the molecular scale or at the nanoscale. Thus, this chapter serves as a base for further discussions about improvements in non-viral gene delivery.