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Published on: June 14, 2017
Drug target discovery using retroviruses
Magnus Blø1, David R Micklem, James B Lorens
1University of Bergen, Bergen, Department of Biomedicine, Jonas Lies vei 91, N-5009, Bergen, Norway +47 55 58 67 76 ; +47 55 58 63 60 ; jim.lorens@biomed.uib.no.
Abstract:
Contemporary drug target discovery relies on a continuum of genetic and chemical-based screening technologies. These approaches conflate pharmaceutical and genetic principles, providing a conceptual platform that links dominant genetics with drug action. Thus, phenotypic genetic screens using vector-expressed dominant genetic effectors - trans-acting molecules that modulate gene function, such as peptides or RNA interference triggers - can reveal genes whose inhibition engenders a therapeutic effect. The correlation of this genetic inhibition with a specific protein activity defines a drug target candidate. Retroviruses provide a unique opportunity to stably deliver a variety of dominant genetic effectors to mammalian cells in a flexible predetermined fashion and are a favoured system for phenotypic screening. Here, the authors review recent innovations and approaches to therapeutic target discovery using retroviral vectors.
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