In Vitro Selection of pH-Activated DNA Nanostructures.
We report the first in vitro selection of DNA nanostructures that switch their conformation when triggered by change in pH. Previously, most pH-active nanostructures were designed using known pH-active motifs, such as the i-motif or the triplex structure. In contrast, we performed de novo selections starting from a random library and generated nanostructures that can sequester and release Mipomersen, a clinically approved antisense DNA drug, in response to pH change. We demonstrate extraordinary pH-selectivity, releasing up to 714-fold more Mipomersen at pH 5.2 compared to pH 7.5. Interestingly, none of our nanostructures showed significant sequence similarity to known pH-sensitive motifs, suggesting that they may operate via novel structure-switching mechanisms. We believe our selection scheme is general and could be adopted for generating DNA nanostructures for many applications including drug delivery, sensors and pH-active surfaces.
Materials Department, University of California at Santa Barbara, Santa Barbara, CA, 93106, USA.
Faye Yi
FY
Fong
Materials Department, University of California at Santa Barbara, Santa Barbara, CA, 93106, USA.|Department of Materials Science and Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
Seung Soo
SS
Oh
Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, CA, 93106, USA.
Craig J
CJ
Hawker
Department of Electrical Engineering and Department of Radiology, Canary Center at Stanford University, 3155 Porter Drive, Stanford, CA, 94305, USA.
H Tom
0000-0001-9443-857X
HT
Soh
D004247:DNA / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures / Q000737:chemistry*
D004247:DNA
DNA structures; controlled release; in vitro selection; nanostructures; pH-responsivity