Researchers have generated a platform that uses combinatorial genetics en masse (CombiGEM) and the CRISPR–Cas9 system for the rapid assembly of barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing.
Researchers have generated a platform that uses combinatorial genetics en masse (CombiGEM) and the CRISPR–Cas9 system for the rapid assembly of barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing.
In this study, the scientists created a platform for the massively parallel screening of barcoded combinatorial gene perturbations in human cells and translated these hits into effective drug combinations. This technology leverages the simplicity of the CRISPR-Cas9 system for multiplexed targeting of specific genomic loci and the versatility of combinatorial genetics en masse (CombiGEM) to rapidly assemble barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing. They applied CombiGEM-CRISPR to create a library of 23,409 barcoded dual guide-RNA (gRNA) combinations and then perform a high-throughput pooled screen to identify gene pairs that inhibited ovarian cancer cell growth when they were targeted.
Here, the scientists leverage the programmability of the CRISPR-Cas9 system for multiplexed targeting of specific genomic loci and the versatility of the combinatorial genetics en masse (CombiGEM) technology to rapidly assemble barcoded combinatorial genetic perturbation libraries that can be tracked with high-throughput sequencing. CombiGEM-CRISPR enables simple, massively parallel screening of barcoded combinatorial gene perturbations in human cells, and the translation of these hits into effective drug combinations. This approach is broadly applicable for performing pooled combinatorial genetic perturbations to map out how the orchestrated action of genes controls complex phenotypes and to translate these findings into novel drug combinations.
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Researchers have generated a platform that uses combinatorial genetics en masse (CombiGEM) and the CRISPR–Cas9 system for the rapid assembly of barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing.