“Global Transcriptional Response to CRISPR/CAS9-AAV6 Based Genome Editing” Matches Transcriptional Response to Specific Small Molecule Perturbations

Abstract

Cromer et al. [1] recently reported global transcriptional changes occuring in cells in response to CRISPR/Cas9 gene editing. Using a CD34+ hematopoietic and progenitor stem cell model, they observed differentially expressed genes enriched for immune, stress and apoptotic processes following treatment with a CRISPR/Cas9-AAV6 genome-editing system. Following treatment with Cas9s mRNA they observed transcriptional changes enriched for viral response as well as a downregulation of metabolic and cell cycle processes. Similarly, they observed a downregulation of metabolic processes in response to electroporation. Surprisingly, no enrichment for viral response genes was observed following treatment with AAV6 while minor transcriptional changes enriched for DNA damage signature occurred in response to Cas9/sgRNA ribonucleoprotein.