Selection of DNA nanoparticles with preferential binding to aggregated protein target

Laura E. Ruff, Ajay A. Sapre, Justin S. Plaut, Elisabeth De Maere, Charlotte Mortier, Valerie Nguyen, Kevin Separa, Sofie Vandenbogaerde, Laura Vandewalle, Sadik C. Esener, Bradley T. Messmer

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

High affinity and specificity are considered essential for affinity reagents and molecularly-targeted therapeutics, such as monoclonal antibodies. However, life's own molecular and cellular machinery consists of lower affinity, highly multivalent interactions that are metastable, but easily reversible or displaceable. With this inspiration, we have developed a DNA-based reagent platform that uses massive avidity to achieve stable, but reversible specific recognition of polyvalent targets. We have previously selected these DNA reagents, termed DeNAno, against various cells and now we demonstrate that DeNAno specific for protein targets can also be selected. DeNAno were selected against streptavidin-, rituximab-and bevacizumab-coated beads. Binding was stable for weeks and unaffected by the presence of soluble target proteins, yet readily competed by natural or synthetic ligands of the target proteins. Thus DeNAno particles are a novel biomolecular recognition agent whose orthogonal use of avidity over affinity results in uniquely stable yet reversible binding interactions.

Original languageEnglish (US)
Article numbere96
JournalNucleic acids research
Volume44
Issue number10
DOIs
StatePublished - Jun 2 2016

ASJC Scopus subject areas

  • Genetics

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    Ruff, L. E., Sapre, A. A., Plaut, J. S., De Maere, E., Mortier, C., Nguyen, V., Separa, K., Vandenbogaerde, S., Vandewalle, L., Esener, S. C., & Messmer, B. T. (2016). Selection of DNA nanoparticles with preferential binding to aggregated protein target. Nucleic acids research, 44(10), [e96]. https://doi.org/10.1093/nar/gkw136