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Publication : A versatile in??vivo platform for reversible control of transgene expression in adult tissues.

First Author  Taguchi J Year  2025
Journal  Stem Cell Reports Volume  20
Issue  1 Pages  102373
PubMed ID  39642874 Mgi Jnum  J:386068
Mgi Id  MGI:8329718 Doi  10.1016/j.stemcr.2024.11.003
Citation  Taguchi J, et al. (2025) A versatile in vivo platform for reversible control of transgene expression in adult tissues. Stem Cell Reports 20(1):102373
abstractText  Temporal control of transgenes has advanced biomedical interventions, including in vivo reprogramming, often utilizing the doxycycline (Dox)-mediated Tet-ON system. Here, we developed the Dox-mediated Tet-ON or complementary Tet-OFF counterpart to thoroughly investigate spatial and temporal transgene regulation in adult tissues, revealing inherent limitations and unexpected capabilities of each system. In stark contrast with the Tet-ON system, which was effective only in particular tissues and cell types, primarily epithelial cells, the Tet-OFF system proved capable of gene induction across diverse cell types. Despite the drawback of the Tet-OFF system in inducibility and tunability identified in our study, we demonstrated that use of tetracycline (Tc) effectively addresses these issues, possibly through its pharmacologic properties. Our data suggest that the Tc-mediated Tet-OFF system not only enables more versatile control of transgene expression but also offers a more biocompatible alternative for in vivo applications such as tissue regeneration and organismal rejuvenation.
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