ReviewCell systems2022
The sound of silence: Transgene silencing in mammalian cell engineering.
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Review in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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129citing papers in PubMed
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Who cites it
129 citing papers in PubMed.
- Silencing of optogenetic and chemogenetic transgenes in human iPSCs involves promoter methylation and methylation-independent mechanisms.Epigenetics · 2026Article
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- Programmable promoter editing for precise control of transgene expression.Nature biotechnology · 2026Article
- A CHO-Derived Matrix Attachment Region Enhances Transgene Dosage, SATB1 Recruitment, and Monoclonal Antibody Expression in a Dual-Promoter Vector System.Molecular biotechnology · 2026Article
- Multichannel genomic recording of biological information with ENGRAM.Nature protocols · 2026Review
- Promoter editing generates stable setpoints of gene expression.Nature biotechnology · 2026Article
- Heritable transgenic schistosomes as a living platform for SARS-CoV-2 neutralizing antibody secretion.Nature communications · 2026Article
- Compound delivery of eVLPs enhances prime editing for targeted genome engineering and high-throughput screening.Cell genomics · 2026Article
- eVLP compound delivery breaks the prime editing efficiency ceiling.Cell genomics · 2026Article
- A stable and potent buffalo EF1α1 promoter for robust gene expression in mammalian systems.Transgenic research · 2026Article
- Expanding Transposase Technology to Regulatory Noncoding RNAs for Stable Expression in CHO Cells.Biotechnology journal · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- BASELINE: a CRISPR base editing platform for mammalian-scale single-cell lineage tracing.Nucleic acids research · 2026Article
- Capturing the dynamics of STAT6 macrophage polarization using bioluminescence temporal signatures.Cell systems · 2026Article
- High-throughput measurements of protein domain functions using magnetic separation.Nature protocols · 2026Review
- Minicircle DNA Vaccines: Overcoming Delivery and Expression Barriers in Next-Generation Immunization.Vaccines · 2026Review
- Image-based, pooled phenotyping reveals multidimensional, disease-specific variant effects.Cell · 2026Article
- Programming T cells for intercellular genome editing.bioRxiv : the preprint server for biology · 2026Article
- Interleukin-10-engineered mesenchymal stem/stromal cells exhibit robust immunomodulatory effects in vitro and in vivo.Stem cell research & therapy · 2026Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors.
Alan CabreraDepartment of Bioengineering, Rice University, Houston, TX 77005, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Hailey I Edelstein *Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA; The Eli and Edythe Broad CIRM Center, Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
Fokion Glykofrydis *Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033-9080, USA.
Kasey S Love *Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sebastian Palacios *Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Josh Tycko *Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Meng Zhang *Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Champaign, Urbana, IL 61801, USA.
Sarah LenschDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Cara E ShieldsWallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA.
Mark LivingstonDepartment of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Huimin ZhaoDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Champaign, Urbana, IL 61801, USA.
Karmella A HaynesWallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA.
Leonardo MorsutDepartment of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033-9080, USA.
Yvonne Y ChenDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA 90095, USA.
Ahmad S KhalilBiological Design Center and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
Wilson W WongBiological Design Center and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
James J CollinsDepartment of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033-9080, USA; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Susan J RosserSchool of Biological Sciences, University of Edinburgh, Edinburgh, UK.
Karen PolizziDepartment of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK; Imperial College Centre for Synthetic Biology, South Kensington Campus, London, UK.
Michael B ElowitzDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
Martin FusseneggerDepartment of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel 4058, Switzerland; Faculty of Science, University of Basel, Mattenstrasse 26, Basel 4058, Switzerland.
Isaac B HiltonDepartment of Bioengineering, Rice University, Houston, TX 77005, USA.
Joshua N LeonardCenter for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA; The Eli and Edythe Broad CIRM Center, Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA.
Lacramioara BintuDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Kate E GallowayDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Tara L DeansDepartment of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: tara.deans@utah.edu.
Funding
Mapping Technology DevelopmentU54DK107965 · NIDDK · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BELMONT, ANDREW STEVEN · 2015 to 2019
$8.6MHigh throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4MMolecular Circuits in the Hematopoietic Stem Cell NicheRC2DK120535 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI COLLINS, JAMES J, DALEY, GEORGE Q · 2020 to 2024
$8.2MDynamics of chromosome organization and chromatin states in single cellsU01DK127420 · NIDDK · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI CAI, LONG, ELOWITZ, MICHAEL B · 2020 to 2024
$5.7MSynthetic toolkit for precision gene expression control and signal processing in mammalian cellsR01EB029483 · NIBIB · HARVARD UNIVERSITY · PI Ahmad Samir Khalil · 2020 to 2026
$5.0MDesign-driven engineering of robust mammalian sense-and-respond functions: from parts to programsR01EB026510 · NIBIB · NORTHWESTERN UNIVERSITY · PI Neda Bagheri, Joshua Nathaniel Leonard · 2018 to 2026
$3.7MSingle-cell analysis and synthetic control of mammalian chromatin dynamics and gene regulationR35GM128947 · NIGMS · STANFORD UNIVERSITY · PI Lacramioara Bintu · 2018 to 2026
$3.1MSynthetic gene sensors and effectors to redirect organoid developmentR01EB030946 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELTA, CALIN, KEMP, MELISSA LAMBETH · 2021 to 2024
$2.6MProgrammed Differentiation Circuits for Organoids using Meso-MicrofluidicsR01EB025256 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI CARR, PETER ANDREW · 2018 to 2021
$2.4MEngineered platelets for the targeted destruction of circulating tumor cells - Administrative SupplementDP2CA250006 · NCI · UNIVERSITY OF UTAH · PI DEANS, TARA LYNN · 2019 to 2022
$2.4MSynthetic development: dissection of morphogenetic programs via reconstructive and perturbative approachesR35GM138256 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MORSUT, LEONARDO · 2020 to 2024
$2.1MMultiscale tools and approaches for understanding and engineering cell-fate transitionsR35GM143033 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GALLOWAY, KATE ELIZABETH · 2021 to 2025
$1.9MNCI NIH HHS DP2 CA250006NCI NIH HHS R21 CA232244NHGRI NIH HHS R56 HG012206NHGRI NIH HHS UM1 HG009402NIBIB NIH HHS R01 EB025256NIBIB NIH HHS R01 EB026510NIBIB NIH HHS R01 EB029483NIBIB NIH HHS R01 EB030946NIBIB NIH HHS R21 EB030772NIDDK NIH HHS K00 DK126120NIDDK NIH HHS RC2 DK120535NIDDK NIH HHS U01 DK127420NIDDK NIH HHS U54 DK107965NIGMS NIH HHS R01 GM129011NIGMS NIH HHS R35 GM128947NIGMS NIH HHS R35 GM138256NIGMS NIH HHS R35 GM143033NIGMS NIH HHS R35 GM143532Wellcome Trust
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.
Indexed as
Gene Regulatory NetworksGenetic EngineeringAnimalsCell CommunicationMammalsTransgenesgenome engineeringmammalian synthetic biologysynthetic gene circuit stabilitytransgene silencing
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