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In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
Chemically Evolved XNAzyme Platforms for Effective In Vivo Gene Regulation
Jun Wang1, Jiansong Zhou1,2, Yimin Zhou1,3,4,5
1Institute of Biomedical Research, Yunnan University, Kunming, China.
Small (Weinheim an Der Bergstrasse, Germany)
|July 22, 2026
Summary
Chemically evolved xeno-nucleic acid enzymes (XNAzymes) show improved RNA cleavage efficiency and stability. This versatile platform enables programmable mRNA silencing and miRNA targeting in biological systems.
Area of Science:
- Biochemistry
- Molecular Biology
- Synthetic Biology
Background:
- DNAzymes are nucleic acid catalysts for RNA cleavage.
- Their use in biological systems is limited by low efficiency and stability.
Purpose of the Study:
- To chemically evolve the 8-17 DNAzyme into XNAzymes with enhanced catalytic activity and stability.
- To demonstrate XNAzyme functionality for programmable RNA regulation in mammalian cells and zebrafish embryos.
Main Methods:
- Rational modification of sugar and backbone components in the DNAzyme catalytic core.
- Terminal modifications to enhance nuclease resistance and reduce degradation.
- Testing XNAzyme activity and gene silencing in mammalian cells and zebrafish embryos.
Main Results:
- Optimized XNAzymes show up to a 14-fold increase in catalytic activity under near-physiological conditions.
- XNAzymes exhibit enhanced nuclease resistance and reduced degradation.
- XNAzymes successfully silence exogenous and endogenous mRNAs, cleave oncogenic miRNA, and induce gene-specific developmental alterations in zebrafish.
Conclusions:
- Chemical evolution of the catalytic core is a viable strategy to enhance nucleic acid enzyme performance.
- XNAzymes represent a versatile platform for programmable RNA regulation in complex biological environments.
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