The sound of silence : Transgene silencing in mammalian cell engineering
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Cell systems - 13(2022), 12 vom: 21. Dez., Seite 950-973 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cabrera, Alan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.12.2022 Date Revised 22.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.cels.2022.11.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM350608083 |
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| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a genome engineering | |
| 650 | 4 | |a mammalian synthetic biology | |
| 650 | 4 | |a synthetic gene circuit stability | |
| 650 | 4 | |a transgene silencing | |
| 700 | 1 | |a Edelstein, Hailey I |e verfasserin |4 aut | |
| 700 | 1 | |a Glykofrydis, Fokion |e verfasserin |4 aut | |
| 700 | 1 | |a Love, Kasey S |e verfasserin |4 aut | |
| 700 | 1 | |a Palacios, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Tycko, Josh |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Lensch, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Shields, Cara E |e verfasserin |4 aut | |
| 700 | 1 | |a Livingston, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Ron |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Huimin |e verfasserin |4 aut | |
| 700 | 1 | |a Haynes, Karmella A |e verfasserin |4 aut | |
| 700 | 1 | |a Morsut, Leonardo |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yvonne Y |e verfasserin |4 aut | |
| 700 | 1 | |a Khalil, Ahmad S |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Wilson W |e verfasserin |4 aut | |
| 700 | 1 | |a Collins, James J |e verfasserin |4 aut | |
| 700 | 1 | |a Rosser, Susan J |e verfasserin |4 aut | |
| 700 | 1 | |a Polizzi, Karen |e verfasserin |4 aut | |
| 700 | 1 | |a Elowitz, Michael B |e verfasserin |4 aut | |
| 700 | 1 | |a Fussenegger, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Hilton, Isaac B |e verfasserin |4 aut | |
| 700 | 1 | |a Leonard, Joshua N |e verfasserin |4 aut | |
| 700 | 1 | |a Bintu, Lacramioara |e verfasserin |4 aut | |
| 700 | 1 | |a Galloway, Kate E |e verfasserin |4 aut | |
| 700 | 1 | |a Deans, Tara L |e verfasserin |4 aut | |
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