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Selection of DNA nanoparticles with preferential binding to aggregated protein target
Laura E Ruff1, Ajay A Sapre2, Justin S Plaut2
1UCSD Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA bmessmer@ucsd.edu.
Nucleic Acids Research
|March 13, 2016
Summary
Researchers developed DNA-based reagents (DeNAno) that use massive avidity for stable, reversible molecular recognition. These DeNAno reagents offer a novel approach to biomolecular interactions, distinct from traditional high-affinity methods.
Area of Science:
- Biochemistry
- Molecular Biology
- Biotechnology
Background:
- Traditional affinity reagents like monoclonal antibodies rely on high affinity and specificity.
- Natural biological systems often utilize lower affinity, multivalent interactions for stable yet reversible binding.
Purpose of the Study:
- To develop a DNA-based reagent platform (DeNAno) leveraging massive avidity for stable, reversible polyvalent target recognition.
- To demonstrate the selection and efficacy of DeNAno reagents against specific protein targets.
Main Methods:
- Selection of DeNAno reagents against beads coated with model protein targets (streptavidin, rituximab, bevacizumab).
- Assessment of binding stability over time and in the presence of soluble target proteins.
- Evaluation of competitive displacement by natural or synthetic ligands.
Main Results:
- DeNAno reagents demonstrated stable binding to protein targets for extended periods (weeks).
- Binding remained unaffected by soluble target proteins, indicating high specificity.
- Reversible binding was confirmed through competition assays with specific ligands.
Conclusions:
- DeNAno particles represent a novel class of biomolecular recognition agents.
- The platform utilizes avidity over affinity, achieving unique stable yet reversible binding interactions.
- This approach offers an alternative to high-affinity reagents for specific molecular targeting.
