Nucleic acid delivery: Where material sciences and bio-sciences meet

Advances in biotechnology have led to an accelerated discovery of macromolecular therapeutics such as peptides, proteins and polynucleotides. These macromolecules can be targeted against a variety of diseases, each requiring delivery to a well-defined compartment of the body. As such therapeutics are often prone to degradation before reaching their target site, or do not reach their target site at all, they often require a special formulation. This review focuses on several types of materials that are currently under investigation for the delivery of nucleic acid therapeutics and aims to pinpoint the limitations of these materials with the ultimate goal to identify the material challenges which, in our opinion, will constitute a new generation of ‘intelligent’ materials for nucleic acid delivery. Such ‘intelligent’ materials should be able to sense and respond to environmental changes. The generated response to these environmental changes should give the material new properties that favor the intracellular delivery of their payload. Besides dealing with material properties, we especially aim to focus on the biological barriers such intelligent materials will have to deal with when used for the delivery of nucleic acids. Furthermore, we briefly discuss the advanced light microscopy techniques that are often used to visualize and quantify the steps of the delivery process of nucleic acids.