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On the Horizon

Leading news, knowledge, and industry trends in genetic research

Screening

14 result(s)





The clinical success rate of new oncology drugs is only 3.4% compared to 20.9% in other disease types (Wong et al, 2018). One contributing factor to this issue is the testing systems used, with two-dimensional (2D) monolayer assay formats as the traditional mainstay of high throughput screening. Although 2D monolayer assays have identified many successful drugs, it is increasingly recognised that they do not accurately model key aspects of the three-dimensional (3D) tumour environment. Therefore, the adoption of high throughput screening approaches using 3D assays to complement 2D approaches could substantially improve prediction of clinical outcomes and reduce the high failure rate of cancer drugs in clinical trials.



A revolution is under way in functional genomics which is spearheaded by the CRISPR-Cas9 system and its application to pooled genetic screening. Remarkable new tools, made possible by dCas9, are coming to fruition that will allow for a new kind of interrogation of gene function, allowing us to ask more sophisticated questions about the biology of drug targets.


The cellular DNA damage response (DDR) is an essential safeguard against cancer. Upon activation, the DDR can limit tumor progression at the early stages by inducing senescence or cell death. When this defense fails tumors are able to develop. However, with time, tumors accumulate more mutations in DNA repair proteins as cancers progress. The efficiency of DDR plays an essential role in the effectivity of cytotoxic treatments. Currently much research is focused on identifying the DDR mechanisms involved in cancers and how these dysfunctional processes can be utilized against tumor growth.


In a paper published on Nature.com in Scientific Reports, Horizon Discovery have conducted a detailed analysis of CRISPR-Cas9 sensitivity (drop-out) screening to come up with a highly improved and optimized platform. In our analysis, we used a custom ultra-complex sgRNA library and capitalized on Horizon's streamlined screening pipeline to evaluate fundamental aspects of functional genomic screening.