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Pooled Phenotypic CRISPR Screening Enables the Identification of Synergistic Drug Combinations for Cancer Therapy

4 Feb 2019

Single agent therapies have often limited clinical benefit, therefore identifying targets that synergize with a given drug is crucial for identifying combination therapy approaches that can maximize treatment efficiency. Cancer drugs, such as Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitors, often lead to proliferative arrest rather than cell death, leaving a reservoir of live tumor cells, some of which might be resistant to the drug or lead to the development of drug resistance. Identifying targets that can induce cell death under these circumstances could be used to eliminate cancer cells and to prevent or delay the development of drug resistance.

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CRISPR Screening Services

CRISPR Screening Services Horizon offers comprehensive CRISPR screening services from screen design and cell line selection to sophisticated bioinformatics analysis of the screen results. Our best-in-class CRISPR KO (knockout), CRISPRi (interference) and CRISPRa (activation) screening platforms can significantly advance our customers’ drug development programs by offering the highest quality and highest confidence in their screening results. Data analysis services, including sample preparation, Next-Gen Sequencing, and hit calling, can be provided for users of Edit-R Lentiviral sgRNA Pooled Screening Libraries. Simply provide whole cell pellets for each of your samples and we’ll do the rest. We can also help with the NGS data analysis and hit calling for data created using the Edit-R Pooled sgRNA Indexing PCR and Sequencing Primer Kits. Types of CRISPR Screen Expertise includes whole-genome and custom targeted drug resistance and sensitivity screens, synthetic lethality target discovery screens and complex phenotypic screens using a FACS-based readout. We have optimized 50+ cell lines for CRISPR screening and have completed over 300 screens to date. We offer a choice of CRISPR screen types depending on the expression effect you require: CRISPR KO screening with complete loss of gene expression provides the maximal window for phenotypic effect and high statistical power for hit discovery CRISPRi screening represses expression rather than completely knocking out the target gene and is ideally suited to study druggability and to evaluate the function of genes that when knocked-out are essential or that are amplified CRISPRa screening amplifies gene expression in its endogenous context and enables for the first time, to study activation-linked responses on a genome-wide level Dual CRISPRi & CRISPRa screening

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Gene Expression and Molecular CloningMolecular cloning is a set of techniques that utilizes vectors to transfer recombinant DNA into host cells and is an essential tool for investigating the expression of genes and proteins in bacterial or mammalian cells. A variety of vectors optimized for gene cloning and expression in a range of host organisms are available, alongside competent cells for genetic replication. Here, you can explore a range of molecular tools, high-quality genomic and cDNA libraries, premade clones, transformation and transfection reagents and mutagenesis or gene expression detection assays and expression arrays. Find the best gene expression and molecular cloning products in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Gene EditingGene editing is the precise alteration to an organism's DNA, with CRISPR being the most well-known technique. It is used in a wide range of applications, including the development of disease models and gene therapy, and crop improvement. Browse our peer-reviewed product directory to find the best gene editing solutions, compare products, check reviews, and get pricing directly from manufacturers.ScreeningUsing robotics, data processing and control software, liquid handling devices and sensitive detectors, screening allows a researcher to quickly conduct millions of chemical, genetic or pharmacological tests.TherapeuticsTherapeutics are treatments designed to alleviate or cure diseases. These include pharmaceuticals, biologics, and gene therapies, which work by targeting specific disease mechanisms. Advances in personalized medicine and biologics offer new hope for patients with conditions that were previously difficult to treat. Browse our peer-reviewed product directory to find therapeutic solutions for various diseases; compare products, check user reviews, and get pricing directly from manufacturers.Drug DevelopmentDrug development refers to the process of bringing a new drug to market.CRISPRCRISPR technology enables precise editing of genes, allowing scientists to modify DNA at specific locations. This revolutionary tool is used in genetic research, drug development, and gene therapy. CRISPR has applications in agriculture, disease treatment, and creating genetically modified organisms (GMOs). Explore CRISPR solutions in our peer-reviewed product directory; compare products, check reviews, and get pricing directly from manufacturers.Cancer ResearchAlthough cancer is often referred to as a single condition, it actually consists of more than 100 different diseases. Microscopy, mass spectrometry, high throughput sequencing and flow cytometry are some of the most common techniques employed in cancer research labs.

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