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Adding tools to the toolbox
CAMBRIDGE, U.K.—Horizon Discovery, a Cambridge-based personalized medicine pioneer, is kicking off a new partnership with Promega Corp. designed to accelerate the route to therapies based on individuals' genetic makeup.
Financial terms of the partnership have not been disclosed.
The partnership centers on the delivery of endogenous gene reporting capabilities in the form of Promega's luciferase and HaloTag reporter technologies, using Horizon's proprietary homologous recombination-based precision genome editing technology (rAAV GENESIS).
In the collaboration, Horizon's rAAV GENESIS will be used to insert highly sensitive reporter technologies at endogenous genetic loci; to enable high-throughput assays to track protein levels and localization (via luciferase and HaloTag, respectively), or gene-promoter activities (via luciferase) in live cells.
To date, Horizon has applied its rAAV gene-editing platform to reconstitute more than 370 cancer mutations and variations in human cell lines that serve as patient-relevant, predictive in-vitro models of genetic disease.
Additional objectives will be to enable the study of tumor response to anticancer treatments in real time by offering in-vivo xenografts of Horizon's tumorigenic-engineered isogenic cell lines with incorporated Promega reporter tags. Preliminary studies have revealed exceptionally clear images of tumor graft response to targeted molecular therapies.
According to Dr. Paul Morrill, commercial director at Horizon, the long-term collaboration will enable further elucidation of genetic drivers of disease and subsequent development of a new toolbox of targeted therapies.
"For the first time, investigators will be able to directly trace the relationship between protein expression, the interaction of that target protein within its molecular pathway, and how it is encoded by the genome," he says. "The disease models will aid all phases of research and development to more quickly isolate novel drugs with activity toward specific cancer genes and pathways. The reference materials will bring better definition regarding the sensitivity and reproducibility of diagnosing specific mutations in patients, so they can receive the 'right' drug in the future."
Morrill explains that the company sought a strategic partner that shared its end-to-end vision of marrying gold-standard human disease models and pathway reporting system tools to better serve all areas of basic and translational research.
"From a cell biology reporting perspective, Horizon sought the most sensitive pathway reporting reagents currently available and in development, which is a clear strength of Promega," he says. "We also shared a similar vision to support clinical efforts towards better achieving personalized medicine with provision of cellular components from Horizon's genetically defined disease models, such as gDNA and formalin-fixed, paraffin-embedded (FFPE) cell blocks harboring specific cancer mutations that can be used as in-process reference standards for clinical diagnostics."
Dr. Jeffrey L. Kelly, Promega's collaboration project manager and a member of the Collaboration Steering Committee, says combining Horizon and Promega's capabilities makes for a unique and powerful tool set to enable the development of personalized medicine.
"Horizon's scientific leaders have outstanding experience developing innovative technologies into commercially successful human disease models with superior biological relevance," he says. "Promega and Horizon share the commitment to excellence in product design and support, and cultivation of deep, lifelong relationships with customers."
According to Morrill, there is an immediate market for physiologically relevant cellular assays that report endogenous genes and pathways.
"Until GENESIS, researchers settled for ectopic, over-expression systems that put in exogenous copies of genes driven by hyperactive viral promoters," he says. "The field knows these results are often misleading and so immediate and sustained growth success is anticipated for the joint offering."
For the Diagnostic Reference standards, Horizon already is offering these reagents and serving thought-leaders in the field with these missing—yet essential—tools.