RT Journal A1 Serebrenik, Yevgeniy V. A1 Sansbury, Stephanie E. A1 Kumar, Saranya Santhosh A1 Henao-Mejia, Jorge A1 Shalem, Ophir T1 Efficient and flexible tagging of endogenous genes by homology-independent intron targeting JF Genome Research JO Genome Research YR 2019 FD August 01 VO 29 IS 8 SP 1322 OP 1328 DO 10.1101/gr.246413.118 UL http://genome.cshlp.org/content/29/8/1322.abstract AB Genome editing tools have simplified the generation of knock-in gene fusions, yet the prevalent use of gene-specific homology-directed repair (HDR) templates still hinders scalability. Consequently, realization of large-scale gene tagging requires further development of approaches to generate knock-in protein fusions via generic donors that do not require locus-specific homology sequences. Here, we combine intron-based protein trapping with homology-independent repair-based integration of a generic donor and demonstrate precise, scalable, and efficient gene tagging. Because editing is performed in introns using a synthetic exon, this approach tolerates mutations in the unedited allele, indels at the integration site, and the addition of resistance genes that do not disrupt the target gene coding sequence, resulting in easy and flexible gene tagging.