Title:DNA-Based Drug Carriers: The Paradox of a Classical “Cargo” Material Becoming a Versatile “Carrier” to Overcome Barriers in Drug Delivery
VOLUME: 22 ISSUE: 9
Author(s):Robert Getts and Silvia Muro
Affiliation:5115 Plant Sciences Building, University of Maryland, College Park, MD, 20742, USA.
Keywords:DNA-built drug carriers, DNA-carrier targeting and intracellular transport, DNA nanoparticles, DNA dendrimers, DNA
liposomes, DNA origami, DNA cages.
Abstract: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.
