Biomod/2014/ASU

DNA antibodies

Abstract

Antibodies are one of the immune system’s most amazing tools for fighting pathogens. They are multivalent proteins, and they are the product of a recombinatory process, which gives them the potential to bind to a wide variety of different targets. Our goal is to use the power and flexibility of DNA nanotechnology to develop a multivalent binding surface that would mimic natural antibodies. We want to base such a structure on a DNA tile, or origami, in order to exploit the straightforward and reliable self-assembly process of these nanostructures. Therefore, we designed a tile that is able to host up to 4 binding sites (aptamers). The characterization of the tile binding properties is performed with a test target protein, human alpha-thrombin, and some aptamers known to bind to it. We apply then SELEX methodologies to coordinately evolve aptamers located at nearby sites on the DNA tile. What we would like to achieve as a result of the evolution process is a “DNA surface” with a quaternary structure that will possibly increase the range of conformations beyond what is achievable with single-stranded aptamers. We propose that the end product will show significantly enhanced affinity and selectivity for its target. In parallel to the experimental approach, we are setting up computational methods, including Molecular Dynamics simulations, to model and further understand the protein-tile interactions.

Goals

Our goal is to establish a method for the production of a multivalent, coordinated aptamer surface on a DNA tile. Such a product would be useful in linking heteroelements to larger DNA structures for use in a variety of applications. 

Multivalence

Multivalence is the property of having multiple domains of attachment to a target. IgG antibodies exhibit a divalent behavior, meaning that they have two domains which can attach to antigens. This allows them to have a much higher affinity for

Coordinated

Coordinated means that this

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