Whole genome CRISPR KO screening enables you to discover the genes that alter response to your compound.
Sub-groups of the patient population may carry mutations in specific gene(s) that affect the response of that individual to a therapeutic. By individually knocking out each of ~19,000 genes, you can identify the genes that alter resistance or sensitivity to your compound.
Horizon has optimized 35+ cell lines for the standard CRISPR KO screen offering called ResponderSCREEN.
Choose 1, 2 or 4 cell lines from our pre-optimized panel, provide us with your compound and you will receive a list of genes that are important for your drug activity.
Apply the data for patient stratification to:
- Maximize the success of your drug development program
- Reduce time to drug approval with improved trial design
- Improve patient outcomes
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*Compound dosage selection available upon request
- 1, 2 or 4 cell lines from Horizon’s list of 35+ pre-optimized cell lines
- CRISPR KO screen using Horizon’s whole genome sgRNA library (~19,000 genes)
- +/- one compound treatment (Client defined concentration)*
- Comprehensive bioinformatics analysis
- Average turnaround time: 12-18 weeks
- A list of genes of which disruption alter response to the compound of interest
- A final report containing experimental design, all raw & analysed data and conclusions of the study
CRISPR screening workflow
Horizon has licensed the use and commercialisation of CRISPR-Cas9 technology from The Broad Institute, ERS Genomics, Harvard University and Caribou BioSciences.
|Whole genome CRISPR KO resistance screen in A375 melanoma cells|
Purpose: A proof of concept study to identify resistance factors against a BRAF kinase inhibitor Vemurafenib (PLX-4032) in A375 melanoma cells that carry a BRAF V600E gain-of-function mutation.
- GeCKO v2 knockout library: 6 sgRNAs against 19,050 genes (Sanjana et al., 2014)
- Pooled-based approach: lentivirus transduction of the library into cells with antibiotic selection
- Treatment of the edited cell population with Vemurafenib for 14 days
- Cell pellet collection and sample preparation
- Next-generation sequencing and data analysis using an adapted MAGeCK workflow
- Highest ranking genes were MED12, NF1, CUL3, NF2, TADA2B and TADA1, which are known to confer resistance to Vemurafenib.
- Additional hits include members of the STAGA histone acetyl transferase complex (TAFL5/PAF65b) and the Mediator complex (MED23).
Figure 1. Ranking of the hits of the screen by
Download the complete application note