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Targeted Elimination of Tumorigenic Human Pluripotent Stem Cells Using Suicide-Inducing Virus-like Particles.
- Source :
-
ACS chemical biology [ACS Chem Biol] 2018 Aug 17; Vol. 13 (8), pp. 2329-2338. Date of Electronic Publication: 2018 Jul 19. - Publication Year :
- 2018
-
Abstract
- Sensitization to prodrugs via transgenic expression of suicide genes is a leading strategy for the selective elimination of potentially tumorigenic human pluripotent stem cells (hPSCs) in regenerative medicine, but transgenic modification poses safety risks such as deleterious mutagenesis. We describe here an alternative method of delivering suicide-inducing molecules explicitly to hPSCs using virus-like particles (VLPs) and demonstrate its use in eliminating undifferentiated hPSCs in vitro. VLPs were engineered from Qβ bacteriophage capsids to contain enhanced green fluorescent protein (EGFP) or cytosine deaminase (CD) and to simultaneously display multiple IgG-binding ZZ domains. After labeling with antibodies against the hPSC-specific surface glycan SSEA-5, EGFP-containing particles were shown to specifically bind undifferentiated cells in culture, and CD-containing particles were able to eliminate undifferentiated hPSCs with virtually no cytotoxicity to differentiated cells upon treatment with the prodrug 5-fluorocytosine.
- Subjects :
- Antimetabolites pharmacology
Carcinogenesis drug effects
Cell Line
Coliphages chemistry
Drug Carriers chemistry
Flucytosine pharmacology
Green Fluorescent Proteins administration & dosage
Humans
Neoplastic Stem Cells cytology
Neoplastic Stem Cells drug effects
Pluripotent Stem Cells cytology
Pluripotent Stem Cells drug effects
Prodrugs pharmacology
Antimetabolites administration & dosage
Capsid Proteins chemistry
Cell Differentiation drug effects
Drug Delivery Systems
Flucytosine administration & dosage
Prodrugs administration & dosage
Virion chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8937
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- ACS chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 29979576
- Full Text :
- https://doi.org/10.1021/acschembio.8b00490