- First-to-market screening services broaden range of possible study types to address critical gaps in target ID and validation
- CRISPRi screening is better suited to study essential genes and genes amplified in the genome
- CRISPRa screening enables the study of gene activation-linked responses on a genome-wide level
Although functional genomic screening using CRISPR gene knockout technology has provided a powerful and precise way to identify and validate novel drug targets, and to elucidate unknown drug mechanisms, there are some biological studies for which CRISPR knockout screens are not appropriate. Horizon’s novel CRISPRi/CRISPRa screening platform substantially broadens the range of possible studies through the capacity to reduce or increase, rather than completely eliminating gene expression. This enables customers to address critical gaps in target ID and validation as they work to develop novel and more effective drug therapies.
Horizon’s CRISPRi and CRISPRa screening capabilities are based on the Company’s highly optimised CRISPR knockout screening platform, which has been used in over 200 screens to date including for 5 of the top 20 pharma. Using multiple parallel analytical approaches, sophisticated bioinformatics enable clear hit identification from data of outstanding quality, driving the performance of Horizon’s CRISPRi and CRISPRa platforms to show a 10-fold better performance over previously published platforms. Horizon’s customers are already adopting CRISPRi and CRISPRa screening, with the first commercial projects currently underway. Each project is customised according to customer need, offering different types of screens and readouts, and a comprehensive report on conclusion.
Horizon has also developed an enhanced solution that combines both CRISPRi and CRISPRa screening, providing greater confidence in hits identified in genome-wide screens. This combined solution can reveal ‘switch’ like genes that display opposing effects when activated or inhibited in the presence of the drug of interest, bringing the prospect of unambiguous target discovery closer.
Dr. Darrin M Disley, CEO Horizon Discovery, commented “CRISPRi and CRISPRa screening are powerful additions to Horizon’s best-in-class CRISPR knockout screening platform, and demonstrate our leadership in functional genomic screening. These first-to-market platforms will open new, exciting opportunities to identify and validate new drug targets and better understand drug mechanisms to advance our pharmaceutical and biotech customers’ discovery and drug development programmes.
“As a result of Horizon’s recent acquisition of Dharmacon, CRISPRi and CRISPRa screening is now part of a unique mixed product and service portfolio that extends Horizon’s capacity to generate the highest quality data, giving customers the highest level of confidence in their results. Further, non-proprietary insights gained by Horizon during the project can then be fed back into the development of future libraries in a process of continuous improvement.”
More information about Horizon’s CRISPRi and CRISPRa screening platforms and the quality of data that they produce, will be presented in a webinar hosted by The Scientist tomorrow (19 September 2017). Register here
About Horizon’s High-throughput Functional Genomic Screening platform:
Horizon has established a core expertise in functional genomic screening using CRISPR-Cas9, gene trap, and siRNA screening platforms. These techniques are used to explore the function of genes by interrupting their sequence or disrupting the process by which they lead to the generation of protein. In this way, these screens can be used to find and validate novel drug targets, to identify mechanisms of drug resistance or sensitivity, and to aid with patient stratification. Horizon performs these screens in both normal human cell lines and also in haploid cell lines, which represent a simplified and efficient model with which to explore gene function as these cells have only one copy of each gene.
About CRISPRi and CRISPRa screening:
CRISPRi, which induces gene repression, and CRISPRa, which activates gene expression, provide new and exciting applications for CRISPR screening. CRISPRi screening is especially well suited to study the function of genes that when knocked out are essential for cell survival, or that are amplified to provide a functional effect, both classes of genes that are not amenable to CRISPR knockout screens. CRISPRa screening enables, for the first time, the study of activation-linked responses on genome-wide level.
Glossary:
- Bioinformatics: the collection, classification, storage, and analysis of biochemical and biological information especially as applied to molecular genetics and genomics
- CRISPR: A gene editing technology that enables genomic modifications in a wide variety of organisms and tissues with high efficiency
- Genetic screening platform: A platform used by Horizon to identify and validate genes as targets for novel therapeutics using CRISPR based screening and other approaches
- Knockout: Genetic technique in which one of an organism's genes is made inoperative.