ArticleGene therapy2006
Optimization of the Tet-On system for regulated gene expression through viral evolution.
Article in Gene therapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed.
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- Design and evolution of the tetracycline repressor into sulfonylurea herbicide-responsive gene switches for field crops.Nature communications · 2026Article
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- Genetic recording and in situ readout of single-cell signaling memory.Nature chemical biology · 2026Article
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- A chimeric viral platform for directed evolution in mammalian cells.Nature communications · 2025Article
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- Conditional Immortalization Using SV40 Large T Antigen and Its Effects on Induced Pluripotent Stem Cell Differentiation Toward Retinal Progenitor Cells.Stem cells and development · 2025Article
- The PNUTS phosphatase complex controls transcription pause release.Molecular cell · 2024Article
- The BCL11A transcription factor stimulates the enzymatic activities of the OGG1 DNA glycosylase.Biological chemistry · 2024Article
- Reconstructing signaling history of single cells with imaging-based molecular recording.bioRxiv : the preprint server for biology · 2024Article
- A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations.Nature communications · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability to control (trans)gene expression is important both for basic biological research and applications such as gene therapy. In vivo use of the inducible tetracycline (Tc)-regulated gene expression system (Tet-On system) is limited by its low sensitivity for the effector doxycycline (dox). We used viral evolution to optimize this Escherichia coli-derived regulatory system for its function in mammalian cells. The components of the Tet-On system (the transcriptional activator rtTA and its tetO DNA binding site) were incorporated into the human immunodeficiency virus (HIV)-1 genome to control viral replication. Prolonged culturing of this HIV-rtTA virus resulted in virus variants that acquired mutations in the rtTA gene. Some of these mutations enhance the transcriptional activity and dox-sensitivity of the rtTA protein. This improvement was observed with different tetO-containing promoters and was independent of the episomal or chromosomal status of the target gene. Combination of these beneficial mutations resulted in greatly improved rtTA variants that are seven-fold more active and 100-fold more dox-sensitive than the original Tet-On system. Furthermore, some of the new Tet-On systems are responsive to Tc and minocycline. Importantly, these rtTA variants show no activity in the absence of dox. The optimized rtTA variants are particularly useful for in vivo applications that require a more sensitive or more active Tet-On system.
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