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Horizon Discovery Group plc is a UK biotechnology company based in Cambridge[1] founded in 2005 that provides products and services to support research into personalized medicine.

Horizon Discovery also has offices in Cambridge, Massachusetts since acquisition of the CombinatoRx service business (known as the combination high throughput screening (cHTS) business) and related assets from Zalicus Inc. in June 2014 for £4.74m ($8.0m USD).[2]

Horizon Discovery Group plc
Company typePublic limited company
IndustryBiotechnology
Founded2005 (2005)
FounderProf. Alberto Bardelli, Dr. Chris Torrance
Headquarters,
Number of locations
3
Area served
Worldwide
Key people
Darrin Disley (CEO), Ian Gilham (Chairman of Board of Directors, 2014)[3]
Products
Services
Number of employees
80
Website

The company engages in research into human genetic profiles in health and disease as well as the development of targeted therapeutics, with an emphasis on oncology. Using various genome editing technologies, the company modifies the DNA of various cell lines to mimic genetic defects found in the general population which put people at risk of developing specific cancer types, or that predispose them to benefit from a certain cancer treatment. The company supplies products and services hundreds of biotechnology, diagnostic and pharmaceutical companies, and academic research institutes.

In September 2013 Horizon announced 2 major collaborations with Sigma-Aldrich and Harvard University, incorporating the companies' respective nuclease genome-editing technologies into Horizon's GENESIS platform. The first collaboration with Sigma-Aldrich saw the licensing of Zinc Finger Nuclease (ZFN) technology, which provides rapid and efficient knock-out of two or more alleles, complementing the precision of Horizon's proprietary rAAV technology. In the collaboration with Harvard University, Horizon licensed the IP for RNA-guided gene editing system CRISPR, which allows the introduction of a single stranded nick in the genome of mammalian cells, allowing specific gene mutations to be created that are not possible with other nuclease technologies. Their Scientific Advisory Board was expanded in 2014 to include CRISPR experts Dr. Emmanuelle Charpentier, Dr. J. Keith Joung, and Dr. Feng Zhang[4]

In 2014, Horizon entered into a genetic diagnostic test development collaboration with Transgenomic in which Horizon Diagnostic's quantitative molecular reference standards would be used in all existing and future assays developed.[5]

GENESIS Genome-Editing Technology[edit]

rAAV[edit]

Recombinant adeno-associated virus (rAAV) genome editing involves the initiation of homologous recombination by an rAAV vector to allow insertion, deletion or substitiution of DNA sequences into the genome of any mammalian cell, enabling genome editing at single base pair resolution. The high precision of rAAV mediated genome editing allows the accurate modeling of genetic diseases caused by Single-nucleotide polymorphisms or point mutations. rAAV is different from other genome editing technology in the fact that it induces homologous recombination without creating double-strand breaks in the DNA, meaning there is less off target cleavage elsewhere in the genome.

CRISPR (Cas9)[edit]

CRISPR technology makes use of the bacterially derived Cas9 protein, that can introduce double stranded breaks within DNA, the location of which is determined by a specifically designed synthetic guide RNA which directs the cut through hybridization with its matching genomic sequence. Typically this technique can cause off-target cleavage of the DNA, so a modified Cas9 protein is employed which avoids double stranded breaks, instead creating single strand “nicks” that can be exploited to introduce subtle changes in the target gene.

Zinc Finger Nuclease (ZFN)[edit]

ZFN technology licensed from Sigma-Aldrich utilises purpose engineered restriction enzymes called Zinc Finger Nucleases which bind to specific unique DNA sequences in the target genome. Through the creation of double stranded breaks in the target sequence and the utilisation of endogenous DNA repair mechanisms, ZFN technology can create targeted gene deletions, modifications or integrations. When a double-strand break is introduced through heterodimerisation of the DNA in a cell, it stimulates the cell's own DNA repair mechanisms, causing homologous recombination of the DNA strands in the presence of a Repair Template to integrate the gene of interest. In the absence of a repair template, the DNA will undergo Non-Homologous End Joining, resulting in gene deletion at the target site. Nuclease based technologies are particularly efficient at rapid deletion or integration of any allele, as well as the knockout 2 or more alleles and they require no antibiotic selection for cell screening.

X-MAN Cell Lines[edit]

Using their genome-editing platform GENESIS, Horizon has created over 500 isogenic X-MAN cell lines. Standing for "Gene-X, Mutant And Normal", the X-MAN lines are two cell lines that are identical save for a targeted genetic modification based on disease causing mutations found in patients. These cell lines allow for the study of normal vs. diseased biology in a more controlled way, as single mutations can be investigated as opposed to patient-derived cancer cell lines which may have multiple genomic mutations that have led to their phenotype, which can act as confounding variables in basic research and drug discovery. Isogenic cell lines are used in the identification or validation of novel drug targets, or the identification, development and prescription of targeted or ‘personalized’ medicines.

These cell lines are currently being used worldwide in academic and industry centers to understand the effects that individual or compound genetic mutations have on drug activity, patient responsiveness, and resistance, allowing tailoring of new treatments towards specific disease biomarkers and in the design of smaller, faster and more risk-free clinical trials by enabling pre-selection of patients most likely to respond.

In addition to X‐MAN cell lines, Horizon provides GENESIS and X‐MAN derived products and services, with industrial applications in: biopharmaceutical process optimization; clinical diagnostic development; drug discovery & development; and the provision of reference standards for genomic‐based clinical research platforms.

Awards[edit]

Year Award Ceremony Award
2014 European Mediscience Awards Emerging Star Award
Santander Breakthrough 50 Breakthrough 50 Winners
2013 East of England Business Awards Biomedtech Company of Year
Scrip Awards 2013 Licensing Deal of the Year
Deloitte Technology Fast 50 Fastest Growing Biotechnology Company in the UK
Deloitte Technology Fast 500 Ranked 7th Fastest Growing Biotechnology Company
Tech City Future Fifty Programme
The Scientist The Scientist’s Top 10 Innovations
Personalized Medicine World Conference Most Promising Company
2012 Queen's Awards for Enterprise International Trade[6]
2011 East of England Business Awards Business of the Year
2010 East of England Business Awards Young Company of the Year award
Cambridge Phenomenon Award Bioscience Company of the Future award
2009 East of England Business Awards Killer Technology Company
UK iAwards Best technology start-up
2008 Medical Futures Innovation Awards Overall winner of the Best Business Innovation Awards

References[edit]

  1. ^ Horizon Discovery | Contact Us Retrieved on September 5, 2014
  2. ^ "Horizon Discovery Group plc Completes Acquisition of CombinatoRx Service Business and Assets from Zalicus Inc." Press release, 02/06/2014
  3. ^ Horizon Discovery Board of Directors Retrieved on September 24, 2014
  4. ^ "Horizon Discovery Adds Three Eminent CRISPR Experts to its Scientific Advisory Board." Press release, 05/08/2014
  5. ^ "Genetic Diagnostic Tests on the Horizon in Transgenomic Collab". News: Molecular Diagnostics. Gen. Eng. Biotechnol. News (paper). Vol. 34, no. 4. p. 32.
  6. ^ "http://www.queensawardsmagazine.com/." Queen’s Awards for Enterprise. Retrieved on September 19, 2013

External links[edit]

Category:Biotechnology companies of the United Kingdom Category:Research support companies