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
{"title":"The sound of silence: Transgene silencing in mammalian cell engineering.","authors":"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","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":54348,"journal":{"name":"Cell Systems","volume":null,"pages":null},"PeriodicalIF":9.0000,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880859/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Systems","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cels.2022.11.005","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
Cell SystemsMedicine-Pathology and Forensic Medicine
CiteScore
16.50
自引率
1.10%
发文量
84
审稿时长
42 days
期刊介绍:
In 2015, Cell Systems was founded as a platform within Cell Press to showcase innovative research in systems biology. Our primary goal is to investigate complex biological phenomena that cannot be simply explained by basic mathematical principles. While the physical sciences have long successfully tackled such challenges, we have discovered that our most impactful publications often employ quantitative, inference-based methodologies borrowed from the fields of physics, engineering, mathematics, and computer science. We are committed to providing a home for elegant research that addresses fundamental questions in systems biology.