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- Title
IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish.
- Authors
Hong, Jeongkwan; Lee, Jae-Geun; Sohn, Kyung-Cheol; Lee, Kayoung; Lee, Seoee; Lee, Jinyoung; Hong, Jihye; Choi, Dongju; Hong, Yeseul; Jin, Hyo Sun; Choi, Dae-Kyoung; Lee, Su Ui; Kee, Yun; Jung, Jangham; Bae, Young-Ki; Hwang, Ran Hee; Hur, Gang Min; Lee, Jeong-Soo; Ro, Hyunju
- Abstract
Though various transgene expression switches have been adopted in a wide variety of organisms for basic and biomedical research, intrinsic obstacles of those existing systems, including toxicity and silencing, have been limiting their use in vertebrate transgenesis. Here we demonstrate a novel QF-based binary transgene switch (IQ-Switch) that is relatively free of driver toxicity and transgene silencing, and exhibits potent and highly tunable transgene activation by the chemical inducer tebufenozide, a non-toxic lipophilic molecule to developing zebrafish with negligible background. The interchangeable IQ-Switch makes it possible to elicit ubiquitous and tissue specific transgene expression in a spatiotemporal manner. We generated a RASopathy disease model using IQ-Switch and demonstrated that the RASopathy symptoms were ameliorated by the specific BRAF(V600E) inhibitor vemurafenib, validating the therapeutic use of the gene switch. The orthogonal IQ-Switch provides a state-of-the-art platform for flexible regulation of transgene expression in zebrafish, potentially applicable in cell-based systems and other model organisms. Hong et al. describe a new transgene expression system, IQ-Switch, and its variants and characterize their applications in cell culture and zebrafish systems. They show that IQ-Switch system has several advantages over the previous inducible transgene expression switches, including the low toxicity, tunability of expression levels and low levels of gene silencing.
- Subjects
BRACHYDANIO; TRANSGENE expression; GENE silencing; MEDICAL research; GENES; ACTIVATION (Chemistry); CELL culture
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02923-3