Figure 5.
CRISPRoff targeting of MGMT in primary GBM. (A) Western blots against MGMT protein in monoclonal (SF7996) or polyclonal (SF14259, SF14346, SF14590, SF14599) populations of patient-derived primary GBM cultures at the indicated number of days following delivery of CRISPRoff and the indicated sgRNA(s). (B) Crystal violet assay of cell viability 7 days following cell seeding and TMZ treatment (replenished every 3 days) at the indicated concentrations for SF7996 primary GBM. Quantification of cell growth (right). Scale bar = 1000 µm. (C) Propidium iodide cell cycle analysis of SF7996 cells treated with TMZ. P value = 2 tailed Student’s t-test for S-phase compared to sgScrambled 20 µM TMZ condition, n = 3 biological replicates. (D) Brightfield light micrographs of CRISPRoff-modified primary GBM cultures (SF14259, SF14346, SF14590, SF14599) 15–35 days following cell seeding, corresponding to the time at which vehicle-treated cells reached confluency. TMZ was replenished every 3 days during culture. Integrated intensity from live cells was quantified (right) for each cell type. (E) Apoptosis assay of primary GBM cultures 7 days following cell seeding and TMZ treatment. P value = 2 tailed Student’s t-test compared to cognate sgScrambled.
