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CRISPR-mediated biocontainment

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1
Cory J Smith
  • Function : Author
Parastoo Khoshakhlagh
  • Function : Author
Raphael Ferreira
  • Function : Author
Marc Güell
  • Function : Author
Khaled Said
  • Function : Author
Ramazan Yildiz
  • Function : Author
Matthew Dysart
  • Function : Author
Stan Wang
  • Function : Author
David Thompson
  • Function : Author
George M Church
  • Function : Author
  • PersonId : 1030371

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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Dates and versions

hal-03027524 , version 1 (27-11-2020)

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Oscar Castanon, Cory J Smith, Parastoo Khoshakhlagh, Raphael Ferreira, Marc Güell, et al.. CRISPR-mediated biocontainment. 2020. ⟨hal-03027524⟩
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