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In Vitro Selection of pH-Activated DNA Nanostructures
Faye Yi Fong1, Seung Soo Oh1,2, Craig J Hawker3
1Materials Department, University of California at Santa Barbara, Santa Barbara, CA, 93106, USA.
Angewandte Chemie (International Ed. in English)
|November 4, 2016
Summary
Researchers developed novel DNA nanostructures that change shape with pH. These structures can capture and release a drug, Mipomersen, with high pH selectivity, suggesting new mechanisms for drug delivery and sensors.
Area of Science:
- Biotechnology
- Nanotechnology
- Molecular Biology
Background:
- Existing pH-responsive DNA nanostructures often rely on known motifs like i-motifs or triplexes.
- Designing novel pH-switchable DNA nanostructures is challenging.
Purpose of the Study:
- To develop de novo DNA nanostructures with pH-triggered conformational changes.
- To create nanostructures capable of sequestering and releasing the drug Mipomersen based on pH.
- To explore novel pH-sensitive DNA structures beyond known motifs.
Main Methods:
- In vitro selection from a random DNA library.
- Characterization of DNA nanostructure conformation switching.
- Quantification of Mipomersen release at different pH levels.
Main Results:
- Successfully selected DNA nanostructures that alter conformation in response to pH changes.
- Demonstrated high pH selectivity, releasing up to 714-fold more Mipomersen at pH 5.2 compared to pH 7.5.
- Identified novel pH-sensitive nanostructures lacking similarity to known pH-active motifs.
Conclusions:
- The developed DNA nanostructures offer a novel approach for pH-triggered drug delivery.
- The selection strategy is general and applicable to various applications, including sensors and active surfaces.
- The findings suggest the existence of new structure-switching mechanisms in DNA nanostructures.
