title: Selection of DNA nanoparticles with preferential binding to aggregated protein target.
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.
authors.affiliation: UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA bmessmer@ucsd.edu.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Ruff
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Ajay A
authors.initials: AA
authors.lastname: Sapre
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Plaut
authors.affiliation: Department Vesalius, Hogeschool Ghent, Ghent 9000, Belgium.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: De Maere
authors.affiliation: Department Vesalius, Hogeschool Ghent, Ghent 9000, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mortier
authors.affiliation: UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Separa
authors.affiliation: Department Vesalius, Hogeschool Ghent, Ghent 9000, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Vandenbogaerde
authors.affiliation: Department Vesalius, Hogeschool Ghent, Ghent 9000, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Vandewalle
authors.affiliation: Department of Nanoengineering, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Sadik C
authors.initials: SC
authors.lastname: Esener
authors.affiliation: UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA bmessmer@ucsd.edu.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Messmer
mesh_terms: D000068258:Bevacizumab / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D000069283:Rituximab / Q000378:metabolism; D019809:Streptavidin / Q000378:metabolism
chemical_list: D008024:Ligands; D011506:Proteins; D000068258:Bevacizumab; D000069283:Rituximab; D004247:DNA; D019809:Streptavidin