Multivalent Binding of Spatially Patterned Nucleic Acid Nanostructures

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DNA, the carrier of genetic information in biology, is increasingly being utilized for non-biological applications. The two strands that link together (hybridize) to form the twisted-shaped genetic material are now designed to link in different ways to form non-biological nanostructures. The precise assembly of nucleic acids through hybridization has revolutionized the field of DNA nanochemistry because it allows one to use simple base-pairing rules to design complex three-dimensional structures. With support from the Macromolecular, Supramolecular and Nanochemistry (MSN) Program of the Division of Chemistry, Professor Khalid Salaita of Emory University is developing increased binding strength and specificity of long strands of DNA to form nanostructures by leveraging the ability to form multiple bonds that reinforce each other. The project focuses on spatially patterned short strands of complementary DNA that function cooperatively to bind a target nucleic acid. Boosting the strength and specificity of targeted DNA binding to specific targets is critical for the application of DNA technology in sensing and diagnostic and therapeutic applications. In the course of conducting this research, graduate and undergraduate students are trained in DNA nanotechnology. K-12 students gain summer research experience and research results are incorporated into science demonstrations and video clips for the general public. The specific goal of this project is to investigate a class of multivalency where orthogonal ligand-receptor pairs are arrayed in a spatially defined manner. This type of “spatially organized heteromultivalency” is not currently employed in DNA nanostructure formation and may offer new strategies for macromolecular and supramolecular design. Professor Salaita seeks to develop synthetic methods and detailed characterization of new types of spatially patterned nucleic acid nanoparticles with enhanced binding capabilities. The hypothesis motivating the effort is that spatial organization of oligonucleotides displayed on the particle surface may lead to a substantial enhancement in the affinity and specificity of binding to a complementary nucleic acid target. An objective of the work is to develop the methodology to spatially pattern nucleic acids on the surface of gold nanoparticles. The binding affinity and specificity of patterned particles will be tested as a function of total segment number, segment density, and molecular flexibility of segments. Another objective is to create patterned liposomal particles. The impact of patterning geometry and anchoring chemistry will be investigated by measuring the full thermodynamic binding constants for these constructs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.