Genome-Wide Genetic Screening in Mammalian Cells Using TALE Libraries

Genome-wide screens to identify genes connected to a phenotype of interest have been performed using RNAi libraries and recently CRISPR-Cas9 libraries. However, both approaches are limited by inherent disadvantages including off-target effects and inefficient gain-of-function screenings. Recently, we introduced an assembly method to efficiently construct TALE (transcription activator-like effectors) libraries which cover all possible combinations of the nucleotides, and demonstrated genome-wide screening experiments in yeast cells. In this study, we constructed biased TALE libraries to target desired motifs and subsequently performed genome-wide screens in human cells to probe for desired change in phenotype.