Gene editing and gene modulation technologies support drug discovery

Horizon Discovery has developed a broad range of gene editing and gene modulation technologies that enable scientists to gain a greater understanding of gene function and apply this knowledge to the development of novel biotherapeutics, gene therapies and diagnostic workflows. This article reviews recent developments at the company.

Headquartered in Cambridge, UK and with offices in the US and Japan, Horizon Discovery Group plc specializes in the application of gene editing and gene modulation technologies that support drug discovery and development within the global life sciences sector, offering a portfolio of tools and services to help scientists gain a greater understanding of gene function, identify genetic drivers behind human disease, and deliver biotherapeutics, cellular and gene therapies for precision medicine as well as for the development and validation of diagnostic workflows. The company’s solutions are designed to enable almost any gene to be altered, or its function modulated, in human and other mammalian cell lines.

Its clients include leading academic institutes, global pharmaceutical and biotechnology companies, and clinical diagnostic laboratories. Horizon says that its insight into the challenges faced by these organizations enables it to focus its efforts on the development of innovative solutions that not only differentiate its offering, but that also fuel development of the next wave of precision medicines.

Horizon Discovery is now offering an arrayed CRISPR knockout screening service for primary human B cells, cells that are freshly isolated from donors and known to be difficult to study in the lab. Pictured is a B-lymphocyte antibody-producing immune cell. (Image from Shutterstock © Kateryna Kon)

Gene knockout and gene activation studies

Earlier this month (July 2020), the company introduced its stably expressing Cas9 and dCas9-VPR cell lines to help accelerate gene knockout and gene activation experiments, respectively. The cell lines are optimized to work alongside the company’s Edit-R predesigned synthetic single guide RNA (sgRNA) and CRISPRa guide RNA, offering researchers a complete solution to simplify and streamline CRISPR gene editing and modulation workflows.

Horizon’s Cas9 and dCas9-VPR stable cell lines were generated using its Edit-R Lentiviral particles with a blasticidin resistance cassette and are provided in pooled format. The cell lines are QC-verified and validated to ensure stable expression and functionality of Cas9 or dCas9-VPR endonuclease in a range of common cell backgrounds. Both cell lines are available in the same background to enable loss-of-function and gain-of-function studies to be performed in parallel without the need to engineer a cell line specifically for this purpose. Horizon says that removing the time-intensive step of generating a stable cell line and the cost associated with purchasing a nuclease could help researchers increase R&D productivity and allow novice users to gain a better understanding of the CRISPR workflow.

Production of highly complex proteins

In a separate recent development, in May of this year, biopharmaceuticals CDMO Rentschler Biopharma SE and Horizon signed a commercial licence agreement under which Horizon’s cGMP-compliant CHOSOURCE platform will be used in combination with Rentschler Biopharma’s novel in-house process for cell line development for difficult-to-express proteins. Horizon’s gene-edited glutamine synthetase (GS) knockout CHO K1 cGMP-compliant cell line will complement Rentschler Biopharma’s existing service offering, providing a royalty-free, state-of-the-art alternative for the production of highly complex proteins to support researchers from early drug development through to commercial manufacturing.

The two companies say that by entering into the agreement, they aim to empower organizations of all sizes, from large pharmaceutical companies to clinical stage biotechs and early-stage startups, to drive efficiencies in biotherapeutic manufacturing and that Rentschler Biopharma’s integrated platform process, together with Horizon’s cell line, will provide innovative and tailored solutions to translate complex medical research into new biopharmaceuticals, elevating the standard of protein expression and allowing clients to access a robust and flexible approach for designer protein therapeutics from concept to market.

Immunotherapy development

Horizon had earlier announced that the CHOSOURCE platform had played a key role in generating a stable cell line for the development of an immunotherapy for autoimmune diseases with pharmaceutical-grade, stable CHO cells delivering high yields of monoclonal antibody for LAG-3 immunotherapy, enabling Immutep and Batavia Biosciences to reach an important milestone in the preclinical development of the compound. The company’s gene-edited GS knockout CHO K1 cell line expression system, offered by Batavia Biosciences as part of its STEP-mAb service, was used to generate a high yielding cell line for Immutep’s IMP761 product candidate, an agonist antibody targeting the immune checkpoint lymphocyte activation gene LAG-3 which controls the signaling between specific immune cells, T cells and antigen-presenting cells responsible for the adaptive immune response, making it a promising focus for novel cancer therapies or for the treatment of autoimmune conditions such as inflammatory bowel diseases, rheumatoid arthritis, and multiple sclerosis.

In yet another CHOSOURCE platform development, Horizon announced in April this year that it was offering special licensing terms to facilitate rapid access to the CHOSOURCE for the development of COVID-19-related therapeutics and diagnostics. Horizon is already a key supplier for COVID-19-related research as a provider of tools and services to academia and industry in their efforts in the pandemic.

Arrayed CRISPR knockout screening service

Also in April, Horizon announced the addition to its cell-based screening services of an arrayed CRISPR knockout screening service for primary human B cells, cells that are freshly isolated from donors and known to be difficult to study in the lab. One advantage of working with these cells, however, is that it brings scientists one step closer to healthy or diseased micro-environments, enabling them to better understand disease etiology and therapeutic mechanisms and thereby advance drug discovery and development programmes.

Horizon has already applied its gene editing and cell culture expertise to maintain the viability of primary human T cells to enable functional genomic screens and has been delivering data-rich information to customers working in drug discovery and development. Horizon says the new B cell screening service, the first of its kind in the market, will enable researchers to identify genes that affect the function of B cells and examine how this impacts other immune cell types, particularly in infectious diseases, cancer, and auto-immune disorders, such as COVID-19, Burkitt’s lymphoma and multiple sclerosis, respectively.


Further information
Horizon Discovery plc
Cambridge, UK
Ph: +44-1223-976160

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