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DNAzyme 10-23 - Based Nanomachines for Nucleic Acid Recognition
Published on: February 9, 2024
L-DNA-Based Framework Nucleic Acid Nanodevice for Lysosomal ATP Imaging.
Qinghong Huang1, Xiaole Ruan1, Xingnuo Mao1
1State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhang Jiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Researchers developed a novel L-DNA nanodevice for stable, long-term monitoring of lysosomal ATP. This chiral nanodevice overcomes DNA probe degradation, enabling reliable study of organelle energy metabolism and related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Nanotechnology
Background:
- Real-time subcellular biomolecular dynamics are crucial for understanding organellar functions.
- Conventional DNA nanoprobes degrade rapidly in lysosomes, limiting long-term dynamic monitoring.
- Lysosomal ATP monitoring is vital for studying cellular energy metabolism.
Purpose of the Study:
- To develop a nuclease-resistant DNA nanodevice for prolonged intraluminal lysosomal ATP imaging.
- To create an ATP-sensing probe using a chiral L-DNA framework nucleic acid (L-FNA) platform.
- To establish a tool for distinguishing structural presence from functional integrity in nanoprobes.
Main Methods:
- Constructed an L-DNA-based framework nucleic acid (L-FNA) nanodevice with mirror-image chirality for nuclease resistance.
- Integrated an ATP-responsive aptamer module into the L-FNA platform to create the L-FNA-apt probe.
- Compared the intracellular retention and functional integrity of L-FNA-apt with conventional D-DNA probes in living cells.
Main Results:
- L-FNA exhibited a 7-fold longer intracellular retention half-life (17.6 h vs 2.5 h) compared to D-DNA.
- L-FNA-apt maintained functional integrity for over 24 hours, significantly longer than D-FNA-apt (6 hours).
- Demonstrated sustained responsiveness of L-FNA-apt to energy stress in living cells for at least 24 hours.
Conclusions:
- The L-FNA nanodevice provides intrinsic nuclease resistance, enabling prolonged lysosomal ATP monitoring.
- L-FNA-apt serves as a reliable tool for studying organelle energy metabolism and related diseases.
- This framework distinguishes structural presence from functional integrity, advancing nanomedicine and diagnostics.
