ArticleScientific reports2020
Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Application Advances of Lentiviral Vectors: From Gene Therapy to Vaccine Development.Molecular biotechnology · 2026Review
- Targeting organelle function in T cells for cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Targeted UDP-glucose ceramide glucosyltransferase stable overexpression induces a metabolic switch improving cell performance at high cell density.Frontiers in bioengineering and biotechnology · 2025Article
- Review
- CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects.Frontiers in immunology · 2024Review
- Enrichment of transgene integrations by transient CRISPR activation of a silent reporter gene.Molecular therapy. Methods & clinical development · 2023Article
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Development and characterization of an inducible assay system to measure Zika virus capsid interactions.Journal of medical virology · 2022Article
- Anti-Apoptotic c-FLIP Reduces the Anti-Tumour Activity of Chimeric Antigen Receptor T Cells.Cancers · 2022Article
- Article
- MicroRNA-mediated metabolic reprogramming of chimeric antigen receptor T cells.Immunology and cell biology · 2022Article
- Application and Design of Switches Used in CAR.Cells · 2022Review
- Design and characterization of a salicylic acid-inducible gene expression system for Jurkat cells.Journal of biotechnology · 2022Article
- Review
- Compact Bidirectional Promoters for Dual-Gene Expression in a Sleeping Beauty Transposon.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Regulated expression of genetic elements that either encode polypeptides or various types of functional RNA is a fundamental goal for gene therapy. Inducible expression may be preferred over constitutive promoters to allow clinician-based control of gene expression. Existing Tet-On systems represent one of the tightest rheostats for control of gene expression in mammals. However, basal expression in absence of tetracycline compromises the widespread application of Tet-controlled systems in gene therapy. We demonstrate that the order of P2A-linked genes of interest was critical for maximal response and tightness of a chimeric antigen receptor (CAR)-based construct. The introduction of G72V mutation in the activation region of the TetR component of the rtTA further improved the fold response. Although the G72V mutation resulted in a removal of a cryptic splice site within rtTA, additional removal of this splice site led to only a modest improvement in the fold-response. Selective removal of key promoter elements (namely the BRE, TATA box, DPE and the four predicted Inr) confirmed the suitability of the minimal CMV promoter and its downstream sequences for supporting inducible expression. The results demonstrate marked improvement of the rtTA based Tet-On system in Sleeping Beauty for applications such as CAR T cell therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.