Adding tools to the toolbox

Horizon, Promega forge predictive disease model pact

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CAMBRIDGE, U.K.—Horizon Discovery, a Cambridge-basedpersonalized medicine pioneer, is kicking off a new partnership with PromegaCorp. 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 genereporting capabilities in the form of Promega's luciferase and HaloTag reportertechnologies, using Horizon's proprietary homologous recombination-basedprecision genome editing technology (rAAV GENESIS).
In the collaboration, Horizon's rAAV GENESIS will be used toinsert highly sensitive reporter technologies at endogenous genetic loci; toenable high-throughput assays to track protein levels and localization (vialuciferase and HaloTag, respectively), or gene-promoter activities (vialuciferase) in live cells.
To date, Horizon has applied its rAAV gene-editing platformto reconstitute more than 370 cancer mutations and variations in human celllines that serve as patient-relevant, predictive in-vitro models of genetic disease.
Additional objectives will be to enable the study of tumorresponse to anticancer treatments in real time by offering in-vivo xenografts of Horizon's tumorigenic-engineered isogeniccell lines with incorporated Promega reporter tags. Preliminary studies haverevealed exceptionally clear images of tumor graft response to targetedmolecular therapies.
According to Dr. Paul Morrill, commercial director at Horizon,the long-term collaboration will enable further elucidation of genetic driversof disease and subsequent development of a new toolbox of targeted therapies.
"For the first time, investigators will be able to directlytrace the relationship between protein expression, the interaction of thattarget protein within its molecular pathway, and how it is encoded by thegenome," he says. "The disease models will aid all phases of research anddevelopment to more quickly isolate novel drugs with activity toward specificcancer genes and pathways. The reference materials will bring better definitionregarding the sensitivity and reproducibility of diagnosing specific mutationsin patients, so they can receive the 'right' drug in the future."
Morrill explains that the company sought a strategic partnerthat shared its end-to-end vision of marrying gold-standard human diseasemodels and pathway reporting system tools to better serve all areas of basicand translational research. 
"From a cell biology reporting perspective, Horizon soughtthe most sensitive pathway reporting reagents currently available and indevelopment, which is a clear strength of Promega," he says. "We also shared asimilar vision to support clinical efforts towards better achieving personalizedmedicine with provision of cellular components from Horizon's geneticallydefined disease models, such as gDNA and formalin-fixed, paraffin-embedded(FFPE) cell blocks harboring specific cancer mutations that can be used asin-process reference standards for clinical diagnostics."
Dr. Jeffrey L. Kelly, Promega's collaboration projectmanager and a member of the Collaboration Steering Committee, says combiningHorizon and Promega's capabilities makes for a unique and powerful tool set toenable the development of personalized medicine.
"Horizon's scientific leaders have outstanding experiencedeveloping innovative technologies into commercially successful human diseasemodels with superior biological relevance," he says. "Promega and Horizon sharethe commitment to excellence in product design and support, and cultivation ofdeep, lifelong relationships with customers."
According to Morrill, there is an immediate market forphysiologically relevant cellular assays that report endogenous genes andpathways.
"Until GENESIS, researchers settled for ectopic,over-expression systems that put in exogenous copies of genes driven byhyperactive viral promoters," he says. "The field knows these results are oftenmisleading and so immediate and sustained growth success is anticipated for thejoint offering."
For the Diagnostic Reference standards, Horizon already isoffering these reagents and serving thought-leaders in the field with thesemissing—yet essential—tools.

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