Dr. Steven Perrault, Technology Development Fellow at Wyss Institute for Biologically Inspired Engineering, Center for Life Science, Boston, Massachusetts, United States

DNA Nanotechnology in Biomedicine: Addressing Obstacles to Development through Biologically-Inspired Engineering

DNA nanotechnology enables engineering of molecular-scale devices with exquisite control over geometry and site specific functionalization. This capability promises compelling advantages in nanomedicine for the development of new diagnostics and therapeutics. A central challenge to biomedical applications of DNA nanotechnology is the susceptibility of nucleic acids to digestion by nucleases present in in vitro and in vivo environments. DNA nanostructures are also known to activate a potent immune response in vivo. Natural particle systems (i.e. viruses) have evolved mechanisms to overcome these obstacles, including encapsulation of their genome and protein capsid shell in a lipid envelope. Inspired by this, we have developed enveloped DNA nanostructures as a design strategy for biomedical applications. Encapsulation in a lipid membrane confers protection against nuclease digestion and decreases immune activation by over two orders of magnitude. Moreover, the in vivo bioavailability of encapsulated nanostructures is greatly increased in comparison to non-encapsulated controls, which are rapidly degraded and excreted. By establishing a design strategy suitable for biomedical applications, we have provided a platform for the engineering of sophisticated, translation-ready DNA nano-devices.