DNA-Based Drug Carriers: The Paradox of a Classical “Cargo” Material Becoming a Versatile “Carrier” to Overcome Barriers in Drug Delivery

Drug delivery strategies help cope with drawbacks of classical pharmaceuticals, including increasing their solubility, diminishing side effects and improving biodistribution. A multitude of vehicles have been envisioned to this end, encompassing a variety of materials, architectures, and functionalities. DNA-built carriers are relatively new, yet promising devices to help overcome some of the current barriers in drug delivery. Its easy fabrication, reproducibility and tunability make DNA a unique material for building devices ranging from macro-scale depot systems to nano-scale vehicles tailored as nanoparticles, containers, dendrimers, tubes, etc. Although this DNA application is relatively novel and knowledge is building up, current advances suggest great potential. Intracellular delivery is a promising option, whereby access of cargoes (from small molecules to large biotherapeutics) to the cytosol has been demonstrated in many cell types, without apparent side effects or need for additional actuators. This is paradoxical since “natural” DNA cannot access cells and nucleic acids are among the most difficult cargoes to be delivered within cells; yet this property arises from engineering DNA into particular configurations. Their biocompatibility and safety also holds potential, since this natural material is biodegradable and nucleotides are biological metabolites. Using modified nucleotides and properly designing their sequence, along with classical chemical means, make it feasible to tune the stability and degradation rates of DNA devices. Taken together, although much research is still necessary to understand the in vivo behaviour of DNA-based vehicles, the design parameters ruling their optimization, and the biological pathways regulating their function, DNA represents a unique material to help in future drug delivery applications. Keywords: DNA-built drug carriers, DNA-carrier targeting and intracellular transport, DNA nanoparticles, DNA dendrimers, DNA liposomes, DNA origami, DNA cages.