Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens

@article{Morgens2017GenomescaleMO,
  title={Genome-scale measurement of off-target activity using Cas9 toxicity in high-throughput screens},
  author={David Morgens and Michael Wainberg and Evan August Boyle and Oana Ursu and Carlos L. Araya and C. Kimberly Tsui and Michael S. Haney and Gaelen T. Hess and Kyuho Han and Edwin E Jeng and Amy Li and Michael Paul Snyder and William James Greenleaf and Anshul Kundaje and Michael C. Bassik},
  journal={Nature Communications},
  year={2017},
  volume={8}
}
CRISPR-Cas9 screens are powerful tools for high-throughput interrogation of genome function, but can be confounded by nuclease-induced toxicity at both on- and off-target sites, likely due to DNA damage. Here, to test potential solutions to this issue, we design and analyse a CRISPR-Cas9 library with 10 variable-length guides per gene and thousands of negative controls targeting non-functional, non-genic regions (termed safe-targeting guides), in addition to non-targeting controls. We find this… 

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