DNA Nanostructures for siRNA Delivery

Small interfering RNAs (siRNAs) represent an emerging class of versatile nucleic acid drugs for a broad spectrum of genetic and metabolic disorders. Since siRNAs can be developed to silence any target gene with relative ease compared to conventional drugs, there is enormous potential in this therapeutic modality for combating a variety of illnesses. However, its application is limited by low biostability, rapid clearance, and poor biodistribution of naked RNA. This is overcome by employing backbone modifications, conjugation of cell-targeting ligands, and the use of nanocarriers. DNA-based nanostructures are well suited to carry siRNA drugs since the use of DNA as a construction material provides the ability to tune the size, shape, and other morphological features of the nanostructure. DNA nanostructures also allow easy loading of multiple siRNA drugs with stoichiometric precision, enable functionalization with various targeting and tracking agents, and can be designed to deliver siRNA cargo in response to various stimuli. In this review, we provide an overview of recent reports on the use of DNA-based nanostructures to achieve targeted delivery of siRNA in vitro and in vivo. We discuss aspects of nanostructure design for various drug-loading and drug-release strategies and pharmacodynamic and pharmacokinetic properties of DNA nanocarriers and provide a survey of various diseases that have been targeted by siRNA-carrying DNA nanostructures. We also highlight the challenges facing these new-generation nanocarriers in achieving their therapeutic potential and clinical applications.