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Fusion with ARRDC1 or CD63: A Strategy to Enhance p53 Loading into Extracellular Vesicles for Tumor Suppression

Min Liu1, Yu Zhang1, Jianfeng He1,2

  • 1Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.

Biomolecules
|May 24, 2024
PubMed

Insights

Genetic modification of small extracellular vesicles (sEVs) with p53 fusion proteins, specifically ARRDC1-p53 or CD63-p53, enhances their therapeutic potential. These modified sEVs effectively deliver p53, increasing cancer cell apoptosis and reducing proliferation.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Nanomedicine

Background:

  • Small extracellular vesicles (sEVs) are promising for therapy and drug delivery.
  • Genetic modification strategies are key for targeted sEV functionalization.

Purpose of the Study:

  • To investigate the impact of fusing p53 with ARRDC1 or CD63 on sEV generation, p53 loading, and therapeutic efficacy.
  • To evaluate the potential of genetically modified sEVs for targeted cancer treatment.

Main Methods:

  • Overexpression of ARRDC1-p53 (ARP) and CD63-p53 (CDP) in HEK293T cells.
  • Analysis of sEV biogenesis markers (TSG101, LAMP1) and sEV production.
  • Quantification of p53 fusion protein and mRNA loading into sEVs.
  • Assessment of sEV therapeutic efficacy in p53-null H1299 cells, measuring apoptosis and proliferation.

Main Results:

  • Overexpression of ARP or CDP increased p53 mRNA and protein levels.
  • ARRDC1 and CD63 fusions significantly enhanced sEV biogenesis and production.
  • Fusion proteins substantially improved loading of p53 and its mRNA into sEVs.
  • ARP-sEVs and CDP-sEVs effectively delivered p53, inducing apoptosis and reducing proliferation in cancer cells, with ARP-sEVs showing superior efficacy.

Conclusions:

  • ARRDC1 and CD63 modifications enhance sEV functionality for therapeutic applications.
  • Genetic modification of sEVs offers a promising strategy for targeted cancer therapy delivery of p53.
Keywords:
ARRDC1CD63extracellular vesiclesp53tumor

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