Drug target discovery using retroviruses

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.