“If p53 inhibits CRISPR human pluripotent stem cells”, it would do so with Tcells too – and select cells without p53, the guardian of the genome

A PD1 CRISPR knockout-Tcell cancer trial in China resulted in 20/21 deaths. Could this have been due to the p53 response – i.e. p53 deficient cells surviving, as first suggested in this June 2018 paper – a serious hurdle in CRISPR applications.

1. “This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 are toxic and kill most hPSCs”
2. Cells which survived had a defective p53, which would render it susceptible to cancer later on.

A year and a half later (Nov 2019) another pre-print reached the same conclusions (for p53, KRAS and VHL mutant selection)

And this toxicity might very well due to off-targets – which is in the 100ks for any gRNA in our genome.