High-throughput screening of therapeutic combinations against ovarian cancer

Abstract

Applying synergistic drug combinations can increase efficacy of cancer treatment. However, conventional methods for identifying those combinations involve testing of every possible combination including different dosages for each agent, are difficult to scale due to the huge amount of efforts and costs needed. To tackle this problem, we have developed CombiGEM-CRISPR (combinatorial genetics en masse-CRISPR) to enable high-throughput assembly and screening of pair-wise gene combinations. By applying CombiGEM-CRISPR,phenotypes of combinatorial gene knockouts could be used to predict the effects of drug inhibitor combinations targeting the matching gene products. We designed a pair-wise sgRNA library comprising 25,281 combinations for interrogating 52 genes that are overexpressed in ovarian cancers. By pooled evaluation of their effects on cell proliferation, our screening identified new combinations that inhibit ovarian cancer cell growth. Therefore, our work accelerates the discovery of new therapeutic options against ovarian cancer through applying CombiGEM-CRISPR.