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

Jumpei Taguchi, Yosuke Yamada, Sho Ohta, Fumie Nakasuka, Takuya Yamamoto, Manabu Ozawa, Yasuhiro Yamada

Core Laboratory for Developing Advanced Animal Models, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.Core Laboratory for Developing Advanced Animal Models, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. · pubmed

Paper

Abstract

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper discusses a novel system for controlling transgene expression, which could have implications for tissue regeneration and organismal rejuvenation. While it does not directly address the root causes of aging, the potential applications in regenerative medicine and rejuvenation suggest relevance to longevity research. However, the findings appear to be incremental rather than groundbreaking, leading to a moderate impact score.

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