Traptamer screening: a new functional genomics approach to study virus entry and other cellular processes

Historically, the genetic analysis of mammalian cells entailed the isolation of randomly arising mutant cell lines with altered properties, followed by laborious genetic mapping experiments to identify the mutant gene responsible for the phenotype. In recent years, somatic cell genetics has been revolutionized by functional genomics screens, in which expression of every protein‐coding gene is systematically perturbed, and the phenotype of the perturbed cells is determined. We outline here a novel functional genomics screening strategy that differs fundamentally from commonly used approaches. In this strategy, we express libraries of artificial transmembrane proteins named traptamers and select rare cells with the desired phenotype because, by chance, a traptamer specifically perturbs the expression or activity of a target protein. Active traptamers are then recovered from the selected cells and can be used as tools to dissect the biological process under study. We also briefly describe how we have used this new strategy to provide insights into the complex process by which human papillomaviruses enter cells. In traptamer screening, millions of traptamers, artificial transmembrane proteins with randomized hydrophobic segments, are expressed in cells. Biological selection is then used to isolate rare cells that display the desired phenotype because a traptamer binds to a transmembrane protein target. After the gene encoding an active traptamer is recovered from DNA isolated from the selected cells, and the traptamer can be used as a tool to study cell behavior.