A Cellular Stress Response Induced by the CRISPR-dCas9 Activation System Is Not Heritable through Cell Divisions

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalCRISPR Journal
Volume3
Issue number3
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Genetics
  • Biotechnology

Fingerprint Dive into the research topics of 'A Cellular Stress Response Induced by the CRISPR-dCas9 Activation System Is Not Heritable through Cell Divisions'. Together they form a unique fingerprint.

Cite this