Origami Antibodies for Threat Sensing

In this Sequential Phase II project, Parabon NanoLabs will develop and demonstrate a deterministic, computationally-driven process for the design, fabrication, manufacturing, and validation of artificial antibodies created using DNA origami.   Such antibodies will have a wide breadth of medical and defense uses, including the detection of biothreat agents (toxins, viruses and bacteria) as environmental contaminants.  These synthetically produced constructs have the potential for greater specificity and functionality than conventional antibodies and will also eliminate the need for animal care and cold chain requirements associated with current antibody production and storage.  Our approach builds on the preceding Phase II project in which a DNA origami antibody was designed and successfully captured thrombin protein using aptamer binding ligands. Here, we will use novel methods to computationally derive optimal binding interfaces for a particular surrogate protein toxin.  We will also advance our existing computer-assisted design (CAD) software to facilitate the construction of origami to present these binding interfaces, and develop laboratory techniques for large-scale manufacture of origami constructs. The resulting origami antibodies will be characterized as components of surface plasmon resonance, enzyme-linked immunosorbent assay (ELISA) and lateral flow assay tests.