A Cellular Stress Response Induced by the CRISPR-dCas9 Activation System Is Not Heritable Through Cell Divisions. Academic Article uri icon

abstract

  • The CRISPR-Cas9 system can be modified to perform "epigenetic editing" by utilizing the catalytically inactive (dead) Cas9 (dCas9) to recruit regulatory proteins to specific genomic locations. In prior studies, epigenetic editing with multimers of the transactivator VP16 and guide RNAs (gRNAs) was found to cause adverse cellular responses. These side effects may confound studies inducing new cellular properties, especially if the cellular responses are maintained through cell divisions-an epigenetic regulatory property. Here, we show how distinct components of this CRISPR-dCas9 activation system, particularly dCas9 with untargeted gRNAs, upregulate genes associated with transcriptional stress, defense response, and regulation of cell death. Our results highlight a previously undetected acute stress response to CRISPR-dCas9 components in human cells, which is transient and not maintained through cell divisions.

published proceedings

  • CRISPR J

altmetric score

  • 0.25

author list (cited authors)

  • Johnston, A. D., Abdulrazak, A., Sato, H., Maqbool, S. B., Suzuki, M., Greally, J. M., & Simes-Pires, C. A.

citation count

  • 2

complete list of authors

  • Johnston, Andrew D||Abdulrazak, Alali||Sato, Hanae||Maqbool, Shahina B||Suzuki, Masako||Greally, John M||Simões-Pires, Claudia A

publication date

  • June 2020