CRISPR-mediated biocontainment

Castanon, O.; Smith, C. J.; Khoshakhlagh, P.; Ferreira, R.; Guell, M.; Said, K.; Yildiz, R.; Dysart, M.; Wang, S.; Thompson, D.; Myllykallio, H.; Church, G. M.

doi:10.1101/2020.02.03.922146

bioRxiv · 10.1101/2020.02.03.922146

CRISPR-mediated biocontainment

Castanon, O.·Smith, C. J.·Khoshakhlagh, P.·Ferreira, R.·Guell, M.·Said, K.·Yildiz, R.·Dysart, M.·Wang, S.·Thompson, D.·Myllykallio, H.·Church, G. M.

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Abstract

We have exploited the repetitive nature of transposable elements of the human genome to generate synthetic circuits. Transposable elements such as LINE-1 and Alu have successfully replicated in mammalian genomes throughout evolution to reach a copy number ranging from thousands to more than a million. Targeting these repetitive elements with programmable DNA nucleases such as CRISPR-Cas9 rapidly induce extremely high levels of cell death. We use this genotoxic feature to build synthetic biocontainment circuits: CRISPR defense system (CRISPR-DS) capable of preventing CRISPR genome editing, and we introduce the proof-of-concept of CRISPR Safety-Switch, an inducible, stringent and non-leaky kill-switch capable of clearing out cell lines resistant to DNA breaks.

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Castanon, O., Smith, C. J., Khoshakhlagh, P., Ferreira, R., Guell, M., Said, K., Yildiz, R., Dysart, M., Wang, S., Thompson, D., Myllykallio, H., Church, G. M.. 2020-02-04. CRISPR-mediated biocontainment. https://doi.org/10.1101/2020.02.03.922146

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