Targeted Elimination of Tumorigenic Human Pluripotent
Stem Cells Using Suicide-Inducing Virus-like Particles
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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 <i>in vitro</i>. 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