The heterozygous R132H mutation in the metabolic isocitrate dehydrogenase 1 (IDH1) gene is found in 1/3 of adult gliomas, the most common primary malignant brain tumor. Recent studies suggest that the R132H mutation converts to a passenger gene during tumor progression. Instead of targeting the IDH1 mutation itself, we performed a high-throughput screen to identify vulnerabilities in IDH1 mutant glioma cultures. We found that the lead compound beta-lapachone, known to target NAD(P)H quinone dehydrogenase 1, effectively reduced viability of IDH1 mutant glioma cells by driving reactive oxygen species, a known vulnerability of IDH1 mutant gliomas. To assess whether the IDH1 mutation is required for regulation of its hypermethylated state and the response to beta-lapachone, we have utilized CRISPR base-editors to induce and correct the R132H mutation in glioma cells. As a model system, we have also induced R132H mutation in human induced pluripotent stem (iPS) cells. Genetic engineering of glioma cells and human iPS cell will provide new tools to study the role of the R132H mutation in the IDH1 gene in regulating biology in glioma cells.