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In Vitro Selection of pH‐Activated DNA Nanostructures
Author(s) -
Fong Faye Yi,
Oh Seung Soo,
Hawker Craig J.,
Soh H. Tom
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201607540
Subject(s) - dna , nanostructure , in vitro , drug delivery , chemistry , nanotechnology , selectivity , biophysics , combinatorial chemistry , computational biology , biology , biochemistry , materials science , catalysis
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.