Dr. David Smith, Fraunhofer Institute for Cell Therapy and Immunology Leipzig

Using rational design principles, sets of DNA strands and other nucleotide-based materials can be assembled into precise nanostructures of nearly any shape or size. Functional, bio-active ligands such peptides, glycans or small molecules can be attached to nearly any unique location on these structural scaffolds, to generate nanometer-precise spatial arrangements with the spatial resolution of a single base-pair (0.34 nanometers). Since the targets of many ligands are structured, multimeric protein complexes with critical features on the single- or sub-nanometer scale, the level of precision offered by DNA-based fabrication can be used to significantly enhance their bio-activity through the principles of templated multi-/oligovalence. By enforcing geometrical complementarity between arrangements of ligands on the underlying DNA structure and the targeted binding or activation sites on multimeric receptors, functions such as binding, blocking or signaling can be enhanced by several orders of magnitude. We use this highly modular approach in a diverse number of applications such as programming the micromechanics of biological hydrogels [1], interrogating the binding of natural and synthetic epitopes to monoclonal antibodies [2], optimizing virus-neutralizing peptides [3] and enhancing the efficacy of cell-stimulatory peptides [4].

[1] Lorenz et al., Advanced Materials, 2018

[2] Möser et al., in preparation

[3] Issmail, Möser et al., in preparation; PCT/EP2018/063841

[4] Möser et al., Int. J. Mol. Sci, 2018