Horizon Discovery Group plc, a specialist in gene editing and gene modulation technologies, has entered into an exclusive strategic partnership with Rutgers, The State University of New Jersey, to develop and commercialise a novel gene editing technology known as base editing. The technology potentially has applications in the development of new cell therapies and Horizon has stated that it would augment the company’s research tools and services.
Horizon will collaborate with Rutgers to further develop the novel base editing platform from the laboratory of Dr Shengkan Jin, associate professor of pharmacology at Rutgers Robert Wood Johnson Medical School. Horizon has made a non-material payment to Rutgers for an option to exclusively license the technology for use in all therapeutic applications and the company will also fund further research in base editing at Rutgers while undertaking evaluation and proof-of-concept studies.
Base editing is a novel technology platform for engineering DNA with the potential to correct errors or mutations by modifying genes using an enzyme. Compared with currently available gene editing methodologies such as CRISPR/Cas9, which creates ‘cuts’ in the gene and possibly lead to adverse or negative effects, this new technology allows for more accurate gene editing while reducing unintended genomic changes. Horizon says the technology will have a significant impact in enabling cell therapies to be progressed through clinical development and towards commercialisation.
Human diseases: simple causes
The base editing approach derives from the fact that many human diseases have a simple and known cause, ie a single genetic alteration caused through heredity genetics or by an infectious agent. Examples include genetic diseases such as sickle cell anemia and Duchenne muscular dystrophy, as well as infectious diseases such as AIDS and hepatitis B. Despite the clear and simple cause, a cure is understandably difficult because the approved drugs, as well as most drugs under development, target a disease-associated target or protein rather than impacting the disease-causing gene itself. This is largely due to a deficiency in understanding of the etiological cause of disease as well as the lack of effective DNA-targeting technology.
CRISPR gene editing technology allows targeted recognition and modification of specific disease-causing DNA sequences in the genes of cells. However, first generation CRISPR technology generates double-strand DNA breaks and often requires disease tissues or cells to have homologous dependent repair activity to achieve optimum therapeutic effect. As double strand DNA breaks are oncogenic in nature and homologous dependent repair activity is, by and large, absent in diseased tissues, the first-generation CRISPR technology arguably has major hurdles to overcome for developing therapeutic vehicles or agents; in particular for developing in-vivo therapeutics since it could generate potentially oncogenic DNA breaks and usually requires homology-dependent repair activity which is absent in most disease-affected organs.
More accurate gene editing
Base editing has the potential to overcome the issues above by utilising a nuclease-deficient CRISPR protein and an RNA-based recruitment mechanism to guide a non-nuclease DNA modifying enzyme, such as a cytidine deaminase, to the disease-causing gene, where the enzyme effectively corrects or modifies the gene in the disease tissues while minimising the generation of the potential oncogenic DNA breaks. This allows more accurate editing of genes with reduced negative effects due to unintentional genomic changes.
Terry Pizzie, Horizon’s Chief Executive Officer, commented: “Base editing is potentially transformative for all gene editing technologies with the potential to help target many diseases that to date have no treatment. As a world leader in the field of gene editing and gene modulation, both in research and applied markets, we are very excited to partner with Dr Jin and Rutgers University. By extending our scientific and IP capabilities, Horizon will now be able to more fully support our pharma, biotech and academic partners to deliver better cell therapy solutions to patients. As part of our five-year investment strategy, Horizon committed to investing in high-value technologies that maintain our market leadership; base editing technology is a perfect example of that. We look forward to updating on the progress of the partnership and potential future next steps.”
According to Dr Jin, the cytidine deaminase version of the technology alone could potentially be used for developing ex-vivo therapeutics such as gene modified cells for sickle cell anemia and beta thalassemia, HIV resistant cells for AIDS, and over-the-shelf CAR-T cells for leukemia, as well as in-vivo therapeutics for inherited genetic diseases: “The potential is enormous,” he said. “In addition to the ‘simple’ diseases caused by a single genetic alteration event, the therapeutic strategy, in principle, could also be useful for treating diseases where permanently targeting a disease-related gene is beneficial.”
Dr David Kimball, Interim Senior Vice President for Research and Economic Development at Rutgers University, added: “Gene editing technology has truly revolutionised how scientists think about their search for better options and outcomes in the treatment of disease. We look forward to advancing the shared goals of further developing this novel base editing platform and improving human health through this collaboration with Horizon.”
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