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. Author manuscript; available in PMC: 2020 Oct 1.
Published in final edited form as: Nat Chem Biol. 2019 Aug 26;15(10):949–958. doi: 10.1038/s41589-019-0342-2

Fig. 2 |. A subset of endolysosomal trafficking regulators are critical only for toxicity of the noncleavable linker ADC.

Fig. 2 |

a, Schematic for sublibrary targeted screen using anti-CD22-maytansine (noncleavable), anti-CD22-VC-maytansine (cleavable) and free maytansine. The targeted sublibrary was designed, synthesized and lentivirally installed into Cas9-expressing Ramos cells. The Ramos cells were either treated with (1) anti-CD22-maytansine, (2) anti-CD22-VC-maytansine or (3) free maytansine or left untreated. The resulting populations were subjected to deep sequencing and analysis. The screens were performed in duplicate and at 1,000× coverage. b, Comparative analysis of results from anti-CD22-maytansine (noncleavable) and free maytansine sublibrary screens. Signed casTLE scores are reported. c, Comparative analysis of results from anti-CD22-maytansine (noncleavable) and anti-CD22-VC-maytansine (cleavable) sublibrary screens. Signed casTLE scores are reported.