To achieve assay automation and miniaturization, the ISRE activity assay was first automated in 96-well plates and then reformatted for 384-well plates. In the 384-well format, the assay exhibited a near-maximal signal at 8000 cells per well and consistent well-to-well and plate-to-plate reproducibility (Figure S1). In 96-and 384-well formats, signal to background (S/B) ratios, coefficients of variance, and Z9-factors achieved excellent performance in comparison to published standards [17, 18] . Representative results for 2fTGH-ISRE-CBG99 cells treated with IFN-b (1000 U/ml) for 7 h compared to 1% DMSO vehicle alone are provided in Table 1 . The results indicate the development of a quantitative and specific cell-based HTS assay of IFN-responsive gene promoter activity.