Engineering DNA-Functionalized Nanostructures to Bind Nucleic Acid Targets Heteromultivalently with Enhanced Avidity
| Autor: | Victor Pui-Yan Ma, Rong Ma, Brendan R Deal, Khalid Salaita, James T. Kindt, Hanquan Su |
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| Rok vydání: | 2020 |
| Předmět: |
Antisense therapy
Oligonucleotide government.form_of_government Nanoparticle Genomics Nanotechnology DNA General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Article Catalysis Nanostructures 0104 chemical sciences chemistry.chemical_compound Colloid and Surface Chemistry chemistry government Nucleic acid Thermodynamics Avidity Conjugate |
| Zdroj: | J Am Chem Soc |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.0c01568 |
| Popis: | Improving the affinity of nucleic acids to their complements is an important goal for many fields spanning from genomics to antisense therapy and diagnostics. One potential approach to achieving this goal is to use multivalent binding, which often boosts the affinity between ligands and receptors, as exemplified by virus-cell binding and antibody-antigen interactions. Herein, we investigate the binding of heteromultivalent DNA-nanoparticle conjugates, where multiple unique oligonucleotides displayed on a nanoparticle form a multivalent complex with a long DNA target containing the complementary sequences. By developing a strategy to spatially pattern oligonucleotides on a nanoparticle, we demonstrate that the molecular organization of heteromultivalent nanostructures is critical for effective binding; patterned particles have a ~23 order-of-magnitude improvement in affinity compared to chemically identical particles patterned incorrectly. We envision that nanostructures presenting spatially patterned heteromultivalent DNA will offer important biomedical applications given the utility of DNA-functionalized nanostructures in diagnostics and therapeutics. |
| Databáze: | OpenAIRE |
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