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Targeted Elimination of Tumorigenic Human Pluripotent Stem Cells Using Suicide-Inducing Virus-like Particles

Antonio Rampoldi1, Stephen N Crooke2, Marcela K Preininger1,3

  • 1Department of Pediatrics , Emory University School of Medicine and Children's Healthcare of Atlanta , Atlanta , Georgia 30322 , United States.

ACS Chemical Biology
|July 7, 2018
PubMed

Insights

Researchers developed virus-like particles (VLPs) to target and eliminate undifferentiated human pluripotent stem cells (hPSCs) without genetic modification, offering a safer alternative for regenerative medicine applications.

Area of Science:

  • Regenerative Medicine
  • Stem Cell Biology
  • Biotechnology

Background:

  • Transgenic suicide gene therapy is a key strategy for eliminating tumorigenic human pluripotent stem cells (hPSCs) in regenerative medicine.
  • However, transgenic modification carries safety risks, including deleterious mutagenesis.

Purpose of the Study:

  • To develop a non-transgenic method for delivering suicide-inducing molecules specifically to hPSCs.
  • To demonstrate the efficacy of virus-like particles (VLPs) for eliminating undifferentiated hPSCs in vitro.

Main Methods:

  • Engineered Qβ bacteriophage capsids into VLPs containing enhanced green fluorescent protein (EGFP) or cytosine deaminase (CD).
  • Displayed IgG-binding ZZ domains on VLPs for targeted delivery.
  • Labeled VLPs with antibodies against the hPSC-specific surface glycan SSEA-5.
  • Assessed binding specificity to undifferentiated hPSCs and cytotoxicity to differentiated cells.

Main Results:

  • EGFP-containing VLPs specifically bound to undifferentiated hPSCs in culture.
  • CD-containing VLPs effectively eliminated undifferentiated hPSCs when treated with the prodrug 5-fluorocytosine.
  • Minimal cytotoxicity was observed in differentiated cells.

Conclusions:

  • Virus-like particles offer a safe and effective method for targeted elimination of undifferentiated hPSCs.
  • This VLP-based approach provides a promising alternative to transgenic strategies in regenerative medicine.

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