Fig. 1

Target engagement of the lead APOE and TREM2 ASOs in cultured human microglia. A Experimental timelines for target engagement assessment of lead APOE and TREM2 ASOs in cultured iMGL. B,C Relative APOE mRNA levels were measured in cultured isogenic APOE^ε3/ε3 (B) and APOE^ε4/ε4 (C) iMGLs. Cultured isogenic APOE^KO/KO iMGL were used as control. All iMGLs were treated with APOE ASO-1 or ASO-13. CNRQ = Calibrated Normalized Relative Quantities. N = 5. D,E Relative TREM2 mRNA levels were measured in cultured isogenic TREM2^WT/WT (D) and TREM2^R47H/R47H (E) iMGLs. Cultured isogenic TREM2^KO/KO iMGL were used as control. All iMGLs were treated with TREM2 ASO-171 or ASO-192. CNRQ = Calibrated Normalized Relative Quantities. n = 3. F,G Relative secreted APOE protein levels medium were measured in culture media from isogenic APOE^ε3/ε3 (F) and APOE^ε4/ε4 (G) iMGLs treated with APOE ASO-1 or ASO-13. n = 6. H,I Relative soluble and total cellular TREM2 protein levels were measured in culture media and cellular extracts from cultured isogenic TREM2^WT/WT (H) and TREM2^R47H/R47H (I) iMGLs, respectively, treated with TREM2 ASO-171 or ASO-192. n = 4