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- David, Florian, 1981, et al.
(author)
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A Perspective on Synthetic Biology in Drug Discovery and Development - Current Impact and Future Opportunities
- 2021
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In: SLAS Discovery. - : Elsevier BV. - 2472-5552 .- 2472-5560. ; 26:5, s. 581-603
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Research review (peer-reviewed)abstract
- The global impact of synthetic biology has been accelerating, because of the plummeting cost of DNA synthesis, advances in genetic engineering, growing understanding of genome organization, and explosion in data science. However, much of the discipline’s application in the pharmaceutical industry remains enigmatic. In this review, we highlight recent examples of the impact of synthetic biology on target validation, assay development, hit finding, lead optimization, and chemical synthesis, through to the development of cellular therapeutics. We also highlight the availability of tools and technologies driving the discipline. Synthetic biology is certainly impacting all stages of drug discovery and development, and the recognition of the discipline’s contribution can further enhance the opportunities for the drug discovery and development value chain.
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| 2. |
- Scott, Louis, 1987, et al.
(author)
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Genetically Encoded Whole Cell Biosensor for Drug Discovery of HIF-1 Interaction Inhibitors
- 2022
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In: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 11:10, s. 3182-3189
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Journal article (peer-reviewed)abstract
- The heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), is an important anticancer target as it supports the adaptation and response of tumors to hypoxia. Here, we optimized the repressed transactivator yeast two-hybrid system to further develop it as part of a versatile yeast-based drug discovery platform and validated it using HIF-1. We demonstrate both fluorescence-based and auxotrophy-based selections that could detect HIF-1α/HIF-1β dimerization inhibition. The engineered genetic selection is tunable and able to differentiate between strong and weak interactions, shows a large dynamic range, and is stable over different growth phases. Furthermore, we engineered mechanisms to control for cellular activity and off-target drug effects. We thoroughly characterized all parts of the biosensor system and argue this tool will be generally applicable to a wide array of protein-protein interaction targets. We anticipate this biosensor will be useful as part of a drug discovery platform, particularly when screening DNA-encoded new modality drugs.
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