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28 January, 2019 - 10:35 By Kate Sweeney

Horizon extends CRISPR Screening Service to primary human T cells

Horizon Discovery, the Cambridge-based global leader in gene editing and gene modulation technologies, has extended its CRISPR Screening Service to include ex vivo T lymphocytes. 

The service extension meets the requirements of immunology-based research in drug discovery, enabling new gene targets to be identified in biologically and potentially therapeutically relevant settings.

CRISPR screens in primary T lymphocytes have proved challenging, owing to complex issues around the introduction of the screening components and Cas9 in particular. 

Horizon has adapted its established CRISPRko (knockout) platform to address these issues and to deliver a robust screening platform in human T lymphocytes, which will enable complex biological processes, novel targets and more effective drug therapies to be investigated in a therapeutically relevant cell type.

Horizon has added CRISPRko screens in ex vivo T lymphocytes to its established CRISPR screening formats – CRISPRko, CRISPRi (interference) and CRISPRa (activation) – in cancer cell lines. 

The company’s extension of its CRISPRko Screening Service strengthens its existing immuno-oncology platform and reinforces its commitment to supporting researchers working in this rapidly growing field of research.

CEO Terry Pizzie said: “The successful demonstration of primary human T cells in Horizon’s CRISPR screening platforms is a breakthrough format for our clients working in the immuno-oncology space, enabling them to find gene targets and potential therapeutic avenues in an immediately biologically relevant setting rather than having to work through surrogate cell lines. 

“We expect that this approach will allow our customers to save considerable time and resources in downstream validation, helping them to get therapeutics to the clinic faster.”

Horizon has established a core expertise in functional genomic screening using CRISPR-Cas9, gene trap, and siRNA screening platforms. These techniques are used to explore the function of genes by interrupting their sequence or disrupting the process by which they lead to the generation of protein. 

In this way, these screens can be used to find and validate novel drug targets, to identify mechanisms of drug resistance or sensitivity, and to aid with patient stratification. 

Horizon performs these screens in both human cell lines and also in haploid cell lines, which represent a simplified and efficient model with which to explore gene function as these cells have only one copy of each gene.

CRISPRi, which induces gene repression, and CRISPRa, which activates gene expression, provide new and exciting applications for CRISPR screening. CRISPRi screening is especially well suited to study the function of genes that when knocked out are essential for cell survival, or that are amplified to provide a functional effect, both classes of genes that are not amenable to CRISPR knockout screens. 

CRISPRa screening enables, for the first time, the study of activation-linked responses on genome-wide level.

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