The sound of silence: Transgene silencing in mammalian cell engineering

Alan Cabrera; Hailey I. Edelstein; Fokion Glykofrydis; Kasey S. Love; Sebastian Palacios; Josh Tycko; Meng Zhang; Sarah Lensch; Cara E. Shields; Mark Livingston; Ron Weiss; Huimin Zhao; Karmella A. Haynes; Leonardo Morsut; Yvonne Y. Chen; Ahmad S. Khalil; Wilson W. Wong; James J. Collins; Susan J. Rosser; Karen Polizzi; Michael B. Elowitz; Martin Fussenegger; Isaac B. Hilton; Joshua N. Leonard; Lacramioara Bintu; Kate E. Galloway; Tara L. Deans

doi:10.1016/j.cels.2022.11.005

The sound of silence: Transgene silencing in mammalian cell engineering

Alan Cabrera, Hailey I. Edelstein, Fokion Glykofrydis, Kasey S. Love, Sebastian Palacios, Josh Tycko, Meng Zhang, Sarah Lensch, Cara E. Shields, Mark Livingston, Ron Weiss, Huimin Zhao, Karmella A. Haynes, Leonardo Morsut, Yvonne Y. Chen, Ahmad S. Khalil, Wilson W. Wong, James J. Collins, Susan J. Rosser, Karen PolizziMichael B. Elowitz, Martin Fussenegger, Isaac B. Hilton, Joshua N. Leonard, Lacramioara Bintu, Kate E. Galloway, Tara L. Deans^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	950-973
Number of pages	24
Journal	Cell Systems
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/j.cels.2022.11.005
Publication status	Published - 21 Dec 2022

Keywords / Materials (for Non-textual outputs)

genome engineering
mammalian synthetic biology
synthetic gene circuit stability
transgene silencing

Access to Document

10.1016/j.cels.2022.11.005Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

DeansEtalCP2022TheSoundOfSilenceFinal published version, 3.62 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre
Tait, J. & Calvert, J.
BBSRC
14/11/14 → 31/03/22
Project: Research

Cite this

Cabrera, A., Edelstein, H. I., Glykofrydis, F., Love, K. S., Palacios, S., Tycko, J., Zhang, M., Lensch, S., Shields, C. E., Livingston, M., Weiss, R., Zhao, H., Haynes, K. A., Morsut, L., Chen, Y. Y., Khalil, A. S., Wong, W. W., Collins, J. J., Rosser, S. J., ... Deans, T. L. (2022). The sound of silence: Transgene silencing in mammalian cell engineering. Cell Systems, 13(12), 950-973. https://doi.org/10.1016/j.cels.2022.11.005

@article{7a7ab83a52df4ff38874c6025f0ede8c,

title = "The sound of silence: Transgene silencing in mammalian cell engineering",

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.",

keywords = "genome engineering, mammalian synthetic biology, synthetic gene circuit stability, transgene silencing",

author = "Alan Cabrera and Edelstein, {Hailey I.} and Fokion Glykofrydis and Love, {Kasey S.} and Sebastian Palacios and Josh Tycko and Meng Zhang and Sarah Lensch and Shields, {Cara E.} and Mark Livingston and Ron Weiss and Huimin Zhao and Haynes, {Karmella A.} and Leonardo Morsut and Chen, {Yvonne Y.} and Khalil, {Ahmad S.} and Wong, {Wilson W.} and Collins, {James J.} and Rosser, {Susan J.} and Karen Polizzi and Elowitz, {Michael B.} and Martin Fussenegger and Hilton, {Isaac B.} and Leonard, {Joshua N.} and Lacramioara Bintu and Galloway, {Kate E.} and Deans, {Tara L.}",

year = "2022",

month = dec,

day = "21",

doi = "10.1016/j.cels.2022.11.005",

language = "English",

volume = "13",

pages = "950--973",

journal = "Cell Systems",

issn = "2405-4712",

publisher = "Cell Press",

number = "12",

}

Cabrera, A, Edelstein, HI, Glykofrydis, F, Love, KS, Palacios, S, Tycko, J, Zhang, M, Lensch, S, Shields, CE, Livingston, M, Weiss, R, Zhao, H, Haynes, KA, Morsut, L, Chen, YY, Khalil, AS, Wong, WW, Collins, JJ, Rosser, SJ, Polizzi, K, Elowitz, MB, Fussenegger, M, Hilton, IB, Leonard, JN, Bintu, L, Galloway, KE & Deans, TL 2022, 'The sound of silence: Transgene silencing in mammalian cell engineering', Cell Systems, vol. 13, no. 12, pp. 950-973. https://doi.org/10.1016/j.cels.2022.11.005

TY - JOUR

T1 - The sound of silence

T2 - Transgene silencing in mammalian cell engineering

AU - Cabrera, Alan

AU - Edelstein, Hailey I.

AU - Glykofrydis, Fokion

AU - Love, Kasey S.

AU - Palacios, Sebastian

AU - Tycko, Josh

AU - Zhang, Meng

AU - Lensch, Sarah

AU - Shields, Cara E.

AU - Livingston, Mark

AU - Weiss, Ron

AU - Zhao, Huimin

AU - Haynes, Karmella A.

AU - Morsut, Leonardo

AU - Chen, Yvonne Y.

AU - Khalil, Ahmad S.

AU - Wong, Wilson W.

AU - Collins, James J.

AU - Rosser, Susan J.

AU - Polizzi, Karen

AU - Elowitz, Michael B.

AU - Fussenegger, Martin

AU - Hilton, Isaac B.

AU - Leonard, Joshua N.

AU - Bintu, Lacramioara

AU - Galloway, Kate E.

AU - Deans, Tara L.

PY - 2022/12/21

Y1 - 2022/12/21

N2 - 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.

AB - 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.

KW - genome engineering

KW - mammalian synthetic biology

KW - synthetic gene circuit stability

KW - transgene silencing

U2 - 10.1016/j.cels.2022.11.005

DO - 10.1016/j.cels.2022.11.005

M3 - Review article

C2 - 36549273

AN - SCOPUS:85144481170

SN - 2405-4712

VL - 13

SP - 950

EP - 973

JO - Cell Systems

JF - Cell Systems

IS - 12

ER -

The sound of silence: Transgene silencing in mammalian cell engineering

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

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Projects

SynthSys-Mammalian: Edinburgh Mammalian Synthetic Biology Research Centre

Cite this