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In Vitro Selection of pH-Activated DNA Nanostructures.

ABSTRACT: 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.

SUBMITTER: Fong FY

PROVIDER: S-EPMC5392411 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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In Vitro Selection of pH-Activated DNA Nanostructures.

Fong Faye Yi FY Oh Seung Soo SS Hawker Craig J CJ Soh H Tom HT

Angewandte Chemie (International ed. in English) 20161103 49

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 ...[more]

PMID: 27809385

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