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Related Concept Videos

The Proteasome02:18

The Proteasome

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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
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Regulated Protein Degradation02:58

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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
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Designing a Bio-responsive Robot from DNA Origami
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Programmable DNA Origami-Based Protease Device for Precise and Direct Proteins Degradation.

Yue Liu1, Hui-Juan Cheng1, Yi-Shan Liu1

  • 1Laboratory of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.

Journal of the American Chemical Society
|April 4, 2026
PubMed
Summary
This summary is machine-generated.

Researchers developed a DNA origami-based protease device (DOPD) for targeted extracellular protein degradation. This novel system precisely eliminates tumor proteins, offering a new approach to cancer immunotherapy and treatment.

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Area of Science:

  • Biotechnology and Nanomedicine
  • Molecular Biology and Proteomics
  • Cancer Therapeutics and Immunotherapy

Background:

  • Targeted protein degradation is a promising therapeutic strategy but is limited by reliance on endogenous cellular pathways.
  • Existing methods face challenges in safety and universality for treating diseases like cancer.
  • A need exists for external, controllable systems to degrade disease-associated proteins directly.

Purpose of the Study:

  • To engineer a DNA origami-based protease device (DOPD) for direct extracellular degradation of tumor-associated proteins.
  • To create a programmable platform for precise protein degradation, overcoming limitations of endogenous pathways.
  • To evaluate the therapeutic potential of DOPD in cancer treatment and immunotherapy.

Main Methods:

  • Fabrication of a DNA origami six-helix bundle structure with dual-functional layers (catalytic and shielding).
  • Incorporation of a pH-sensitive switch and a recognition module for targeted protease activation.
  • Demonstration of extracellular protein degradation (nucleolin and PD-L1) on tumor cells in vitro and in vivo using a xenograft mouse model.

Main Results:

  • The DOPD successfully assembled proteases and regulated their activity via a shielding layer and pH-sensitive switch.
  • Specific degradation of nucleolin and PD-L1 on tumor cells was achieved under acidic conditions.
  • DOPD exhibited direct cytotoxicity against tumor cells and alleviated immunosuppression in immune cells, showing efficacy in a mouse model.

Conclusions:

  • The DNA origami-based protease device (DOPD) represents a novel, programmable platform for targeted extracellular protein degradation.
  • DOPD effectively degrades tumor-associated proteins, exerting anti-tumor effects and modulating the immune microenvironment.
  • This technology holds significant potential for developing advanced cancer therapeutics and precise protein degradation strategies.