The sound of silence: Transgene silencing in mammalian cell engineering

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 cont...

Full description

Bibliographic Details
Main Authors: Cabrera, Alan, Edelstein, Hailey I, Glykofrydis, Fokion, Love, Kasey S, Palacios, Sebastian, Tycko, Josh, Zhang, Meng, Lensch, Sarah, Shields, Cara E, Livingston, Mark, Weiss, Ron, Zhao, Huimin, Haynes, Karmella A, Morsut, Leonardo, Chen, Yvonne Y, Khalil, Ahmad S, Wong, Wilson W, Collins, James J, Rosser, Susan J, Polizzi, Karen, Elowitz, Michael B, Fussenegger, Martin, Hilton, Isaac B, Leonard, Joshua N, Bintu, Lacramioara, Galloway, Kate E, Deans, Tara L
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Elsevier BV 2023
Online Access:https://hdl.handle.net/1721.1/147792
_version_ 1811093229016186880
author Cabrera, Alan
Edelstein, Hailey I
Glykofrydis, Fokion
Love, Kasey S
Palacios, Sebastian
Tycko, Josh
Zhang, Meng
Lensch, Sarah
Shields, Cara E
Livingston, Mark
Weiss, Ron
Zhao, Huimin
Haynes, Karmella A
Morsut, Leonardo
Chen, Yvonne Y
Khalil, Ahmad S
Wong, Wilson W
Collins, James J
Rosser, Susan J
Polizzi, Karen
Elowitz, Michael B
Fussenegger, Martin
Hilton, Isaac B
Leonard, Joshua N
Bintu, Lacramioara
Galloway, Kate E
Deans, Tara L
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
Cabrera, Alan
Edelstein, Hailey I
Glykofrydis, Fokion
Love, Kasey S
Palacios, Sebastian
Tycko, Josh
Zhang, Meng
Lensch, Sarah
Shields, Cara E
Livingston, Mark
Weiss, Ron
Zhao, Huimin
Haynes, Karmella A
Morsut, Leonardo
Chen, Yvonne Y
Khalil, Ahmad S
Wong, Wilson W
Collins, James J
Rosser, Susan J
Polizzi, Karen
Elowitz, Michael B
Fussenegger, Martin
Hilton, Isaac B
Leonard, Joshua N
Bintu, Lacramioara
Galloway, Kate E
Deans, Tara L
author_sort Cabrera, Alan
collection MIT
description 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.
first_indexed 2024-09-23T15:41:57Z
format Article
id mit-1721.1/147792
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T15:41:57Z
publishDate 2023
publisher Elsevier BV
record_format dspace
spelling mit-1721.1/1477922023-02-01T03:07:15Z The sound of silence: Transgene silencing in mammalian cell engineering Cabrera, Alan Edelstein, Hailey I Glykofrydis, Fokion Love, Kasey S Palacios, Sebastian Tycko, Josh Zhang, Meng Lensch, Sarah Shields, Cara E Livingston, Mark Weiss, Ron Zhao, Huimin Haynes, Karmella A Morsut, Leonardo Chen, Yvonne Y Khalil, Ahmad S Wong, Wilson W Collins, James J Rosser, Susan J Polizzi, Karen Elowitz, Michael B Fussenegger, Martin Hilton, Isaac B Leonard, Joshua N Bintu, Lacramioara Galloway, Kate E Deans, Tara L Massachusetts Institute of Technology. Department of Biological Engineering 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. 2023-01-30T19:56:46Z 2023-01-30T19:56:46Z 2022-12 2023-01-30T19:48:43Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147792 Cabrera, Alan, Edelstein, Hailey I, Glykofrydis, Fokion, Love, Kasey S, Palacios, Sebastian et al. 2022. "The sound of silence: Transgene silencing in mammalian cell engineering." Cell Systems, 13 (12). en 10.1016/j.cels.2022.11.005 Cell Systems Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier
spellingShingle Cabrera, Alan
Edelstein, Hailey I
Glykofrydis, Fokion
Love, Kasey S
Palacios, Sebastian
Tycko, Josh
Zhang, Meng
Lensch, Sarah
Shields, Cara E
Livingston, Mark
Weiss, Ron
Zhao, Huimin
Haynes, Karmella A
Morsut, Leonardo
Chen, Yvonne Y
Khalil, Ahmad S
Wong, Wilson W
Collins, James J
Rosser, Susan J
Polizzi, Karen
Elowitz, Michael B
Fussenegger, Martin
Hilton, Isaac B
Leonard, Joshua N
Bintu, Lacramioara
Galloway, Kate E
Deans, Tara L
The sound of silence: Transgene silencing in mammalian cell engineering
title The sound of silence: Transgene silencing in mammalian cell engineering
title_full The sound of silence: Transgene silencing in mammalian cell engineering
title_fullStr The sound of silence: Transgene silencing in mammalian cell engineering
title_full_unstemmed The sound of silence: Transgene silencing in mammalian cell engineering
title_short The sound of silence: Transgene silencing in mammalian cell engineering
title_sort sound of silence transgene silencing in mammalian cell engineering
url https://hdl.handle.net/1721.1/147792
work_keys_str_mv AT cabreraalan thesoundofsilencetransgenesilencinginmammaliancellengineering
AT edelsteinhaileyi thesoundofsilencetransgenesilencinginmammaliancellengineering
AT glykofrydisfokion thesoundofsilencetransgenesilencinginmammaliancellengineering
AT lovekaseys thesoundofsilencetransgenesilencinginmammaliancellengineering
AT palaciossebastian thesoundofsilencetransgenesilencinginmammaliancellengineering
AT tyckojosh thesoundofsilencetransgenesilencinginmammaliancellengineering
AT zhangmeng thesoundofsilencetransgenesilencinginmammaliancellengineering
AT lenschsarah thesoundofsilencetransgenesilencinginmammaliancellengineering
AT shieldscarae thesoundofsilencetransgenesilencinginmammaliancellengineering
AT livingstonmark thesoundofsilencetransgenesilencinginmammaliancellengineering
AT weissron thesoundofsilencetransgenesilencinginmammaliancellengineering
AT zhaohuimin thesoundofsilencetransgenesilencinginmammaliancellengineering
AT hayneskarmellaa thesoundofsilencetransgenesilencinginmammaliancellengineering
AT morsutleonardo thesoundofsilencetransgenesilencinginmammaliancellengineering
AT chenyvonney thesoundofsilencetransgenesilencinginmammaliancellengineering
AT khalilahmads thesoundofsilencetransgenesilencinginmammaliancellengineering
AT wongwilsonw thesoundofsilencetransgenesilencinginmammaliancellengineering
AT collinsjamesj thesoundofsilencetransgenesilencinginmammaliancellengineering
AT rossersusanj thesoundofsilencetransgenesilencinginmammaliancellengineering
AT polizzikaren thesoundofsilencetransgenesilencinginmammaliancellengineering
AT elowitzmichaelb thesoundofsilencetransgenesilencinginmammaliancellengineering
AT fusseneggermartin thesoundofsilencetransgenesilencinginmammaliancellengineering
AT hiltonisaacb thesoundofsilencetransgenesilencinginmammaliancellengineering
AT leonardjoshuan thesoundofsilencetransgenesilencinginmammaliancellengineering
AT bintulacramioara thesoundofsilencetransgenesilencinginmammaliancellengineering
AT gallowaykatee thesoundofsilencetransgenesilencinginmammaliancellengineering
AT deanstaral thesoundofsilencetransgenesilencinginmammaliancellengineering
AT cabreraalan soundofsilencetransgenesilencinginmammaliancellengineering
AT edelsteinhaileyi soundofsilencetransgenesilencinginmammaliancellengineering
AT glykofrydisfokion soundofsilencetransgenesilencinginmammaliancellengineering
AT lovekaseys soundofsilencetransgenesilencinginmammaliancellengineering
AT palaciossebastian soundofsilencetransgenesilencinginmammaliancellengineering
AT tyckojosh soundofsilencetransgenesilencinginmammaliancellengineering
AT zhangmeng soundofsilencetransgenesilencinginmammaliancellengineering
AT lenschsarah soundofsilencetransgenesilencinginmammaliancellengineering
AT shieldscarae soundofsilencetransgenesilencinginmammaliancellengineering
AT livingstonmark soundofsilencetransgenesilencinginmammaliancellengineering
AT weissron soundofsilencetransgenesilencinginmammaliancellengineering
AT zhaohuimin soundofsilencetransgenesilencinginmammaliancellengineering
AT hayneskarmellaa soundofsilencetransgenesilencinginmammaliancellengineering
AT morsutleonardo soundofsilencetransgenesilencinginmammaliancellengineering
AT chenyvonney soundofsilencetransgenesilencinginmammaliancellengineering
AT khalilahmads soundofsilencetransgenesilencinginmammaliancellengineering
AT wongwilsonw soundofsilencetransgenesilencinginmammaliancellengineering
AT collinsjamesj soundofsilencetransgenesilencinginmammaliancellengineering
AT rossersusanj soundofsilencetransgenesilencinginmammaliancellengineering
AT polizzikaren soundofsilencetransgenesilencinginmammaliancellengineering
AT elowitzmichaelb soundofsilencetransgenesilencinginmammaliancellengineering
AT fusseneggermartin soundofsilencetransgenesilencinginmammaliancellengineering
AT hiltonisaacb soundofsilencetransgenesilencinginmammaliancellengineering
AT leonardjoshuan soundofsilencetransgenesilencinginmammaliancellengineering
AT bintulacramioara soundofsilencetransgenesilencinginmammaliancellengineering
AT gallowaykatee soundofsilencetransgenesilencinginmammaliancellengineering
AT deanstaral soundofsilencetransgenesilencinginmammaliancellengineering