Self-assembled DNA Nanostructures: from Structural Material to Biomedical Nanodevices

Abstract

In addition to being the natural genetic information carrier, DNA can also serve as a versatile material for construction of nanoscale objects. By using the base-pairing properties of DNA, we have been able to mass-produce nano-scale structures in a variety of different shapes, upon which patterns of other molecules can be further specified. The diversity of molecules and materials that can be attached to DNA and the capability of providing precise spatial positioning considerably enhance the attractiveness of DNA for nano-scale construction. A further challenge remains to use these DNA based structures for biomedical applications. As proof-of-concept, a DNA-based nanodevice for multivalent thrombolytic delivery is designed, which intends to employ DNA nanostructures as carriers for the delivery of tissue plasminogen activator (tPA) and plasminogen. Universal modular adapter molecules that can simultaneously bind "down" to the DNA structures and "up" to these thrombolytic drugs are further proposed. We begin with exploring the molecular recognition properties provided by biotin-avidin and aptamer-ligand pairs, and are able to achieve site-specific display of certain protein targets along the DNA nanostructure scaffold. Yet for both of these approaches, only biotinylated or specially selected proteins can be patterned. We further propose to develop single-chain diabodies (scDb) as the adapter molecules. This scDb approach is highly modular and can be extended to assemble virtually any proteins and therapeutic molecules of interests, which at the same time will greatly enhance our molecular toolbox for nanoscale construction.