APPLICATIONS FOR TARGET IDENTIFICATION IN DRUG DISCOVERY AND MORE

CRISPR screens are widely used to uncover novel drug targets. However, they are usually coupled to rather simplistic read-outs, such as cell fitness. At Myllia, we combine CRISPR screening with single-cell RNA sequencing, thus combining CRISPR perturbation with high-content phenotyping. Leveraging fitness, flow cytometry and single-cell transcriptomics read-outs, we enable genome-wide CRISPR drug screens, large-scale FACS-based screens and CROP-Seq screens at single-cell resolution.

Drug target identification & drug target validation

Blue target icon representing drug target identification.

Drug target identification & drug target validation

Target identification is the first step of a drug discovery campaign and begins with a screen identifying possible ‘druggable’ targets and their role in the respective disease. Myllia’s unique CROP-Seq screening technology in combination with the best available cellular models including cancer cells and primary T cells supports the identification and validation of critical genes and pathways driving certain disease states.

Mode of action (MoA) analysis

Screen illustrated as an icon in blue, symbolizing the drug target validation.

Mode of action (MoA) analysis

Understanding how drugs act in the complex environment of a cell remains one of the critical aspects of drug discovery and development. CROP-Seq delivers transcriptional profiles associated with drug action and indicates which genes impact the drug profile, thus providing unique insights into its mechanism of action. It also uncovers genes that modify drug responses, thus paving the way for combination therapy.

Identification of disease-associated gene function and immune pathways

Illustrated DNA in blue for identifying disease-associated gene function.

Identification of disease-associated gene function and immune pathways

Genome-wide association studies (GWAS) have identified thousands of genetic variants that are linked to disease. Unfortunately, many of these loci lie in non-coding regions of the genome. Pinpointing the gene(s) whose expression is regulated by these regions would elucidate novel drug targets that are causally linked to disease. Myllia has built a CRISPR interference (CRISPRi) platform that can map disease-associated variants to genes in an unbiased fashion.

Genetic screening for primary T cell phenotypes

Network icon in to illustrate the primary T cell CRISPR screen subsets identified by computational biology.

Genetic screening for primary T cell phenotypes

Engineering of T-lymphocytes has become a crucial factor driving the development of novel cellular medicines and cancer immunotherapies. However, apart from tumor-associated antigens (TAA) and Chimeric Antigen Receptor (CAR) or T Cell Receptor (TCR) discovery, many T cell-intrinsic features involved in CAR-T cell potency remain elusive. At Myllia, CRISPR screens are performed in primary human T cells to study T cell activation, differentiation and phenotypic plasticity. Utilizing dropout fitness/viability screens, FACS-based screens or CROP-Seq screens at single-cell resolution, we aim to partner with pharmaceutical companies striving to develop the next-generation of CAR-T and TCR-T cell products.

CRISPR screens accelerate drug discovery across many therapeutic areas and help unravel gene regulatory networks in cancer cells and primary human T cells.