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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.
Afiliación
  • Cabrera A; Department of Bioengineering, Rice University, Houston, TX 77005, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Edelstein HI; 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.
  • Glykofrydis F; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033-9080, USA.
  • Love KS; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Palacios S; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Tycko J; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Zhang M; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Champaign, Urbana, IL 61801, USA.
  • Lensch S; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Shields CE; Wallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA.
  • Livingston M; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.
  • Weiss R; Department 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, Cambridg
  • Zhao H; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Champaign, Urbana, IL 61801, USA.
  • Haynes KA; Wallace H. Coulter Department of Biomedical Engineering, Emory University, Atlanta, GA 30322, USA.
  • Morsut L; Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA 90033-9080, USA.
  • Chen YY; Department 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
  • Khalil AS; Biological Design Center and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
  • Wong WW; Biological Design Center and Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
  • Collins JJ; Department 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,
  • Rosser SJ; School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
  • Polizzi K; Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, UK; Imperial College Centre for Synthetic Biology, South Kensington Campus, London, UK.
  • Elowitz MB; Division 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.
  • Fussenegger M; Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel 4058, Switzerland; Faculty of Science, University of Basel, Mattenstrasse 26, Basel 4058, Switzerland.
  • Hilton IB; Department of Bioengineering, Rice University, Houston, TX 77005, USA.
  • Leonard JN; 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.
  • Bintu L; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Galloway KE; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Deans TL; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: tara.deans@utah.edu.
Cell Syst ; 13(12): 950-973, 2022 12 21.
Article en En | MEDLINE | ID: mdl-36549273
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería Genética / Redes Reguladoras de Genes Límite: Animals Idioma: En Revista: Cell Syst Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ingeniería Genética / Redes Reguladoras de Genes Límite: Animals Idioma: En Revista: Cell Syst Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos