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Programmable DNA Nanostructures for hTERT Compartmentalization and Translocation in Living Cells.

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Researchers created artificial DNA condensates to trap human telomerase reverse transcriptase (hTERT) in cancer cells. This DNA nanotechnology inhibits hTERT activity, blocking cell proliferation and offering a new cancer therapy strategy.

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Area of Science:

  • Synthetic biology
  • Biotechnology
  • Molecular oncology

Background:

  • Protein translocation is crucial for cellular function and activity regulation.
  • Controlling protein movement with artificial intracellular compartments is challenging.

Purpose of the Study:

  • To develop a controllable strategy for manipulating protein translocation using artificial DNA condensates.
  • To compartmentalize human telomerase reverse transcriptase (hTERT) and inhibit its activity in cancer cells.

Main Methods:

  • Engineered branched DNA structures with mitochondria-targeting and telomerase-priming functionalities.
  • Triggered strand displacement reaction upon cellular uptake, leading to X-shaped DNA self-assembly.
  • Formation of DNA condensates on mitochondria to capture cytoplasmic hTERT.

Main Results:

  • Successfully formed mitochondria-localized DNA condensates within cancer cells.
  • Disrupted mitochondrial function, increased reactive oxygen species (ROS), and exported hTERT from the nucleus.
  • Specifically captured cytoplasmic hTERT, preventing mitochondrial translocation and inhibiting cancer cell proliferation.

Conclusions:

  • Demonstrated a novel DNA nanotechnology for dynamic intracellular compartmentalization.
  • Provided a controllable method to inhibit hTERT activity and impact cancer cell behavior.
  • Opened new avenues for therapeutic strategies targeting protein translocation in diseases.