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Whether you are looking for a translational research partner or the custom generation of precision functional genomics tools for your research, or you wish to access a Post-Genomic Drug Discovery Toolbox we can help. Explore below to learn how!

Translational Genomics Drug Discovery & Development Drug Manufacture Molecular Reference Standards
Application area Description
High content screening Exposure of cells to chemicals or biological molecules to look for changes in cell morphology, or protein levels and/or localization by image analysis
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Our high-content screening offering involves exposing cells to chemical (e.g. compound libraries) or biological molecules (e.g. RNAi or antibody) and looking for changes in cell morphology, protein levels and/or localization by image capture and analysis.

A key aspect of high-content screening is the ability to study a target gene in its endogenous context. With our GENESIS™ gene-editing program, we have created an extensive menu of genetically-defined X-MAN™ cell lines including many that contain endogenous pathway reporters that allow researchers to follow changes in protein levels/localization. We can also support customer research efforts in this area through specialist 2D and 3D cell-based assay development and compound profiling services. 

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Synthetic lethality Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death, whereas a mutation in only one of these genes does not
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Synthetic lethality is a process that takes advantage of cellular mechanisms whereby the loss of any one of two genes can be compensated by the normal function of the other. By having one gene non-functional a range of other genes can be explored by rendering them non-functional through drug inhibition. When cell death occurs, it indicates that the siRNA or shRNA was interfering with a critical pathway partner of the non-functional gene, suggesting these are potential gene targets for future therapeutics.

We have developed a large panel of genetically-defined X-MAN™ cell lines that can be deployed in cell-based phenotypic screens with siRNA and shRNA libraries designed to represent the drugable genome. The SyntheTx platform can be accessed by partners in a collaborative research or fee for service basis.

Learn more about our target identification platform  

Application Notes Publications

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Posters
Comparative profiling Investigation of the differences between two or more cell states
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Comparative profiling compares multiple samples, often differentiated by disease state, to identify the molecular factors (genetic or epigenetic) which differ between the samples. These genes or proteins can be candidates for therapeutic development.

Multiple samples will come from different genetic backgrounds and it can be difficult to determine precisely which changes are associated with the disease state.

Introducing the genetic changes in a clean genetic background,  as can be achieved using GENESIS™ in creating genetically-defined X-MAN™ cell lines, allows the investigation of the specific changes associated with a precise genetic change using genomic, proteomic, metabolomic and other approaches.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Pathway analysis Identification of the components that comprise signaling pathways and interactions with other pathways
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Biological processes are orchestrated by many specific cellular pathways which consist of interacting genes and proteins. In any given disease state, many of these pathways are altered and the ability to understand these pathways and how the various proteins within it interact can lead to the identification of novel ways to intervene in the pathway signalling.

A crucial element for pathway analysis is that interactions between members of the pathway are at the correct levels. Genetically-defined X-MAN™ cell lines can be created with rAAV GENESIS™ that have target genes tagged with pathway and transcriptional reports at their endogenous loci resulting in relevant expression levels of the protein and interactions with other members of the pathway to be measured. These tagged-proteins can be used to monitor activity of the pathway as well as identifying directly interacting proteins.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes

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Publications

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Posters

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Target validation After a drug target has been identified, a rigorous evaluation occurs to demonstrate that modulation of the target will have the desired effect
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Many novel targets for drug discovery are identified by knocking down their expression with siRNA or shRNA’s.  A standard approach to show that the effect is specific to the gene in which expression is reduced is to rescue the effect by exogenous expression of the cDNA of the target gene. This is not always successful as it is difficult to achieve the correct levels of expression of the cDNA.

The binding site of the siRNA/shRNA can easily be identified and we can use GENESIS™ to create X-MAN™ cell lines that insert multiple point mutations at this binding site to prevent binding of the siRNA/shRNA but not alter the open reading frame of the gene. This will create an allele which is resistant to the effects of degradation. As this allele is expressed at endogenous levels it provides an ideal method to rescue the effects of a siRNA/shRNA and hence validate the target gene. 

Alternatively, GENESIS™ can be used to knock-in activating mutations or knock-out of target to look for phenotype/biomarkers, and to engineer kinase dead cell lines to specifically address whether kinase activity of a putative target is critical.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our target identification platform  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes Publications

  See more...

Posters

  See more...

Tumor microenvironment How a tumor interacts with cells, molecules and blood vessels that surround it
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The complex microenvironment that surrounds a solid tumor can impact not only gene and protein expression but also affect the way drugs will behave. By manipulating in vitro assay conditions, different aspects of the tumor microenvironment can be examined.

X-MAN™ cell lines contain disease-relevant mutations at their endogenous loci. These endogenous mutations can be placed under selective pressure to illicit true disease phenotypes & drug responses. We have developed a large panel of 2D and 3D phenotypic assays and have the specialist equipment and knowledge that allow evaluation of aspects of the tumor microenvironment.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes Publications

  See more...

Posters

  See more...

Specialist in vitro assay Assays investigating specific aspects of cell biology such as oxygen tolerance and cell migration
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When trying to address specific research questions it is critical to use not only patient relevant cell line models but also to apply the most appropriate assay format. 

Genetically-defined human disease models, such as X-MAN™ cell lines can be used across many in vitro assay formats, and in some instances particular assay formats may be required in order to reveal the specific phenotypic consequence of a genetic alteration.  Extensive in vitro assay development expertise can be accessed via Horizon’s contract research group on a fee for service basis.  As well an existing panel of optimized assays, we also have experience with bespoke assay development.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes Publications

  See more...

Posters

  See more...

Resistance mechanisms Identification of mechanisms that cells adopt to overcome specific drugs
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A number of cases, particularly in oncology, have now been identified where a patient’s genetics can impact the efficacy and safety of therapeutics. A key example of this is the variable response of patients with K-Ras mutations to Erbitux and Vectibix, two drugs that target EGFR mutant patient populations in colorectal cancer.  Particularly given the cost of such treatments, it is increasingly important to ensure that drugs are safe and effective and so genetic resistance mechanisms are increasingly being looked for.

Patient-relevant X-MAN™ isogenic cell models have been successful at predicting such genetic-based clinical outcomes for single and combinatorial treatment regimens, guiding focused project development, clinical trial design and the recruitment and marketing/co-marketing of more effective therapeutic regimens.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes Publications

  See more...

Posters

  See more...

Drug repositioning Repurpose an existing drug for a new indication
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Careful study of genomic markers is causing clinical data to be re-examined to understand whether there are subtleties in patient responses to drugs. This is allowing drugs to be re-profiled for new patient populations or indications.  An example is Lithium Chloride, for use in breast cancer types carrying the mutant PI3K gene. 

X-MAN™ cell lines are being used as a powerful and definitive system to explore and predict patient drug-sensitivity and resistance profiles based on their genetics.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Compound screening Performance of chemical, genetic or pharmacological tests on compound libraries to quickly identify active compounds
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Compound screening is a widely-used approach to drug discovery involving the performance of chemical, genetic or pharmacological tests in parallel on compound libraries. Through this process researchers can quickly identify active compounds, antibodies or genes which modulate a particular biomolecular pathway, providing a starting point for the identification of promising lead compounds. Compound screening of large numbers of compounds is known as High Throughput Screening.

Genetically-defined X-MAN™ cell lines can be deployed in these assays to identify novel drug-candidates that selectively impact a chosen genotype. Moreover, by using isogenic cell lines researchers will inherently understand if altering that gene has selective effects on a disease vs. normal cell type – thus feeding the drug discovery process with candidates that have higher chance of success. At Horizon, our screening lab can handle small to medium sized compound (small molecule or RNAi) screening projects on a fee for service basis.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes

  See more...

Publications

  See more...

Posters

  See more...

Patient stratification Identification of patient populations that respond differentially to therapeutics
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Patient stratification involves identifying the subsets within a patient population that respond differently to a given drug. Stratification can be a critical component to transforming a clinical trial from a negative or neutral outcome to one with a positive outcome by identifying the subset of the population most likely to respond to a novel therapy.

A panel of genetically defined X-MAN™ cell lines covering a wide range of human disease genotypes enables drug discovery researchers to determine the optimal patient populations to target with their drug candidates in the expensive clinical trial stage of the drug development process.

The availability of such data enables researchers to determine the full range of sensitive and resistant patient populations to the disease target in clinical trials. This will enable the design of smaller more efficient clinical trials that read-out quicker and be more likely to succeed and reduce the high-rate of attrition currently observed at this critical phase of drug development.

Biomarker discovery and drug profiling can be performed on a fee for service basis.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes

  See more...

Publications

  See more...

Posters
Secondary profiling Profiling lead compounds on their specific therapeutic mechanism of action
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During drug development it is crucial to understand the mode of action of a novel drug. Secondary profiling seeks to understand the mode of action from activity of the drug on its primary target through to a response in a disease model.

By using a panel of genetically-defined X-MAN™ cell lines that contain disease-causing mutations at endogenous loci, the activity of a drug can be profiled as it is developed. This allows the determination of on vs. off-target activity of the drug and so desired activities can be incorporated into the final drug design. 

We can support these efforts on a fee for service basis via performance of detailed mechanism of action assays (e.g. pathway signaling, apoptosis, FACS, IF etc.) to evaluate the mode of action of a drug and we can study on/off target effects. 

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Application Notes Publications

  See more...

Posters

  See more...

Drug combinations Rational combinations of drugs to provide therapy
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Many drugs entering the market have limited efficacy with resistance occurring after a few months of treatment. Combinations of drugs with well-understood modes of action will probably be the future of treatment and we will need to understand which combinations are most suited for specific disease genotypes especially for the treatment of resistant genotypes.

Creation of genetically-defined X-MAN™ cell lines, which contain the disease causing mutations at the endogenous locus, provide a clean system to investigate drug sensitivity, resistance and combinations of drugs which provide efficacy.   We can perform fee for service work looking at different combination assay formats:

  • Simple potentiation assays where one compound in not effective alone
  • Multiplexed formats to look at combinations of  two or more compounds that are individually effective, to see if synergistic when combined.

Learn more about our menu of X-MAN™ cell lines and X-MAN™ Reporter Kits  

Learn more about our contract research services  

If your cell line of interest is not available consider the generation
of a custom cell line  

If your cell line of interest is not available consider generating your own
with GENASSIST™  

Learn more about CombinatoRx™ combination screening services  

Bioproduction Cell based production of biologics
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Bioproduction is the production of biologics-based reagents (typically proteins) in a cell-based system at large volume. A small number of cell lines have been refined for this application, most notably CHO cells, yielding large quantities of high-quality protein.

Efforts are continually underway to further improve yield, quality and purity, and the current focus is on targeted gene editing of CHO cells.  Our GENESIS™ platform is ideal for development of custom CHO cell lines that modify productivity factors.  For example, there are many factors that can limit the ability to produce high levels of biologics including confounding enzymatic activities. We can remove the genes that encode for these limiting factors creating a cell line that can increase the yield/purity of the biologic produced.

Explore our custom Bioproduction cell line production service  

Molecular reference standards FFPE and gDNA controls for Diagnostic assays
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Increasingly, drugs are being mandated to confirm through theranostics that patients must conform to specific genotypes before they are able to receive the drug in order to ensure safety and efficacy.

This has led to a range of molecular diagnostic tests being developed across a broad number of platforms all with the goal of screening patients.  In order to set up an assay in a lab and to make sure that the sensitivity and specificity of these tests is maintained, regular quality control is required.

We have generated a menu of off-the-shelf reference standards capable of being used as controls that are available in defined allelic ratios between mutant and wild-type forms and in gDNA and FFPE formats. 

Learn about Quantitative Molecular Reference Standards  

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