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Lysosome Interference Enabled by Proton-Driven Dynamic Assembly of DNA Nanoframeworks inside Cells
Yuhang Dong1, Feng Li1, Zhaoyue Lv1
1Frontiers Science Center for Synthetic Biology (MOE), Key Laboratory of Systems Bioengineering (MOE), Institute of Biomolecular and Biomedical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, P.R. China.
Angewandte Chemie (International Ed. in English)
|June 22, 2022
Summary
Researchers developed "lysosome interference," a method using DNA nanostructures to modulate lysosome function. This approach enhances gene silencing by protecting nucleic acid drugs from degradation within the lysosome.
Area of Science:
- Biomaterials Science
- Molecular Biology
- Cell Biology
Background:
- Modulating lysosomal function is crucial for controlling cellular processes.
- Lysosomes play a key role in the degradation of intracellular components and delivered therapeutics.
- Developing targeted strategies to interact with lysosomes is an active area of research.
Purpose of the Study:
- To develop a novel method for rationally modulating lysosomal functions using materials chemistry.
- To investigate the potential of DNA nanostructures for lysosome interference.
- To enhance the efficacy of nucleic acid drugs by preventing their lysosomal degradation.
Main Methods:
- Utilized a proton-driven dynamic assembly of a DNA nanoframework with acid-responsive elements.
- Exploited lysosome-mediated endocytosis and lysosomal maturation pathways for cellular uptake.
- Triggered DNA nanoframework aggregation within lysosomes via pH-dependent changes.
Main Results:
- The DNA nanoframework successfully entered lysosomes and formed stable aggregates.
- Proton consumption by the DNA structure reduced lysosomal acidity and hydrolase activity.
- This interference hindered the degradation of nucleic acid drugs, improving gene silencing efficacy.
Conclusions:
- Demonstrated a novel strategy for lysosome interference by coupling material self-assembly with cellular pathways.
- Showcased the potential of programmable DNA nanostructures for targeted intracellular modulation.
- Established a new approach to enhance therapeutic outcomes by controlling lysosomal drug degradation.
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