RT Journal Article
SR Electronic
T1 CRISPR-mediated biocontainment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.03.922146
DO 10.1101/2020.02.03.922146
A1 Oscar Castanon
A1 Cory J. Smith
A1 Parastoo Khoshakhlagh
A1 Raphael Ferreira
A1 Marc Güell
A1 Khaled Said
A1 Ramazan Yildiz
A1 Matthew Dysart
A1 Stan Wang
A1 David Thompson
A1 Hannu Myllykallio
A1 George M. Church
YR 2020
UL http://biorxiv.org/content/early/2020/02/04/2020.02.03.922146.abstract
AB 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.