Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 14, Pages 4654-4658Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201900829
Keywords
deoxyribozymes; DNA machines; gene therapy; hybridization; RNA recognition
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Funding
- overnment of the Russian Federation [08-08]
- Russian Federation for Basic Research [18-34-00898 mol_a]
- NSF CCF [1423219]
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Despite decades of effort, gene therapy (GT) has failed to deliver clinically significant anticancer treatment, owing in part to low selectivity, low efficiency, and poor accessibility of folded RNA targets. Herein, we propose to solve these common problems of GT agents by using a DNA nanotechnology approach. We designed a deoxyribozyme-based DNA machine that can i)recognize the sequence of a cancer biomarker with high selectivity, ii)tightly bind a structured fragment of a housekeeping gene mRNA, and iii)cleave it with efficiency greater than that of a traditional DZ-based cleaving agent. An important advantage of the DNA nanomachine over other gene therapy approaches (antisense, siRNA, and CRISPR/cas) is its ability to cleave a housekeeping gene mRNA after being activated by a cancer marker RNA, which can potentially increase the efficiency of anticancer gene therapy. The DNA machine could become a prototype platform for a new type of anticancer GT agent.
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