Generation of Cell Models
Successful target identification and validation starts with having the right cellular model that reflects the relevant disease processes. Using CRISPR knock-out and knock-in and RNAi technologies or directed target overexpression, we design and generate the right cell model tailored to your target identification and validation project.
Potential parental cell lines are selected according to your project needs; we work with verified immortalized and cancer cell lines, primary cells and induced pluripotent human stem cell (iPSC)-derived cells, and purified immune cells from whole blood. Our biosafety level 2 facilities allow for viral transductions in addition to nucleofection and transfection for transgene expression and generation of stable lines. Co-culture, 2D culture, and 3D culture formats are available.
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Target Screening
Historically, the way that novel drug targets were most often identified involved combing published scientific literature for insights into molecular pathways or genetic variants linked to disease. With recent advances in machine learning, genomics, and functional genomics technologies, novel experimental strategies have become available for discovering original therapeutically relevant targets.
Our functional genomics and analytical and cellular in vitro assay platforms perform target screening campaigns with unbiased approaches to more fully understand the relationship between genotype and phenotype, build disease-relevant models and assays, and enable you to elucidate the mechanisms of action and biological pathways affected in disease.
We offer target screening
- of your cell model of choice (2D or 3D)
- in large-scale pooled or arrayed formats
- using focused custom or whole-genome targeting libraries
- CRISPR: CRISPRn, CRISPRa, CRISPRi, perturb-seq (CRISPR ko and CRISPRi combined with single-cell sequencing)
- RNAi: siRNA or shRNA
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Target Deconvolution
Phenotypic small-molecule screens allow for the unbiased target-independent identification of novel therapeutic drug candidates. Knowledge of the direct drug target, however, greatly aids rational drug design and enables efficient structure–activity relationship studies to be carried out in a chemical optimization program by configuration of target-specific assays. Thus, the subsequent identification of the direct drug target, the target deconvolution, is an important part of phenotypic screening campaigns.
We offer CRISPR-based target screening and proteomics as stand-alones or a combination approach to identify drug targets, an approach we have previously successfully used.
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Target Profiling
To confirm target validity and understand the role of your targets in the proposed therapeutic context, we perform transcriptomic and proteomic profiling; metabolomics, individual gene knock-out, knock-down, and over-expression studies, both in vitro and in vivo; and extensive bioinformatics analyses.
We offer broad target profiling by immunohistochemistry (IHC) based on comprehensive clinical sample collection tumor microarrays (TMAs) comprising the most relevant tumor indications, including histopathology assessment and scoring of expression (H-Score) by pathologist or semi-automated quantification. TMAs are a powerful tool for drug target validation, enabling assessment for target expression in representative patient samples in a tissue context.
Patient sample profiling using TMAs
Whole slide scanning and automated quantification
Indication profiling for early clinical trials
Indication Space Assessment
To identify the most suitable indication for developing your asset, we map the specific indication space for your asset using big data analytical tools. We propose first positioning, indication expansion, repositioning, or repurposing, building on our more than 10 years of experience. We identify the most well-suited proof-of-concept indication for your asset and propose feasible paths forward by identifying the most translational in vivo or ex vivo models. Our track record of projects includes many that found their home in often unexpected indications. The in silico, in vivo, ex vivo, and in vitro studies we perform can be conducted in our labs—or we can orchestrate your studies with third-party partners. We assist you from conceptual drafting to clinical translation and regulatory documentation by de-risking every step.
