An RNA-Cleaving DNAzyme That Requires an Organic Solvent to Function

Tianjun Chang, Guangping Li, Dingran Chang, Ryan Amini, Xiaoni Zhu, Tongqian Zhao, Jimmy Gu, Zhongping Li*, Yingfu Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Engineering functional nucleic acids that are active under unusual conditions will not only reveal their hidden abilities but also lay the groundwork for pursuing them for unique applications. Although many DNAzymes have been derived to catalyze diverse chemical reactions in aqueous solutions, no prior study has been set up to purposely derive DNAzymes that require an organic solvent to function. Herein, we utilized in vitro selection to isolate RNA-cleaving DNAzymes from a random-sequence DNA pool that were “compelled” to accept 35 % dimethyl sulfoxide (DMSO) as a cosolvent, via counter selection in a purely aqueous solution followed by positive selection in the same solution containing 35 % DMSO. This experiment led to the discovery of a new DNAzyme that requires 35 % DMSO for its catalytic activity and exhibits drastically reduced activity without DMSO. This DNAzyme also requires divalent metal ions for catalysis, and its activity is enhanced by monovalent ions. A minimized, more efficient DNAzyme was also derived. This work demonstrates that highly functional, organic solvent-dependent DNAzymes can be isolated from random-sequence DNA libraries via forced in vitro selection, thus expanding the capability and potential utility of catalytic DNA.

Original languageEnglish (US)
Article numbere202310941
JournalAngewandte Chemie - International Edition
Volume62
Issue number42
DOIs
StatePublished - Oct 16 2023

Funding

Funding for this work was provided by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC), the China Scholarship Council (201808410520), National Natural Science Foundation of China (No. U1704241), and National Foreign Expert Program of the Ministry of Science and Technology (G2022004012L).

Keywords

  • Dimethyl Sulfoxide
  • DNAzyme
  • Functional Nucleic Acid
  • In Vitro Selection
  • Organic Solvent

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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