The sound of silence: Transgene silencing in mammalian cell engineering


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Date

2022-12-21

Publication Type

Review Article

ETH Bibliography

yes

Citations

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Data

Abstract

To elucidate principles operating in native biological systems and to develop novel biotechnologies, synthetic biology aims to build and integrate synthetic gene circuits within native transcriptional networks. The utility of synthetic gene circuits for cell engineering relies on the ability to control the expression of all constituent transgene components. Transgene silencing, defined as the loss of expression over time, persists as an obstacle for engineering primary cells and stem cells with transgenic cargos. In this review, we highlight the challenge that transgene silencing poses to the robust engineering of mammalian cells, outline potential molecular mechanisms of silencing, and present approaches for preventing transgene silencing. We conclude with a perspective identifying future research directions for improving the performance of synthetic gene circuits.

Publication status

published

Editor

Book title

Journal / series

Volume

13 (12)

Pages / Article No.

950 - 973

Publisher

Elsevier

Event

Edition / version

Methods

Software

Geographic location

Date collected

Date created

Subject

Mammalian synthetic biology; Transgene silencing; Genome engineering; Synthetic gene circuit stability

Organisational unit

03694 - Fussenegger, Martin / Fussenegger, Martin check_circle

Notes

Funding

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