An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells
© 2020, The Author(s). Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device’s output does n...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/133608 |
| _version_ | 1826217976025579520 |
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| author | Jones, Ross D Qian, Yili Siciliano, Velia DiAndreth, Breanna Huh, Jin Weiss, Ron Del Vecchio, Domitilla |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Jones, Ross D Qian, Yili Siciliano, Velia DiAndreth, Breanna Huh, Jin Weiss, Ron Del Vecchio, Domitilla |
| author_sort | Jones, Ross D |
| collection | MIT |
| description | © 2020, The Author(s). Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device’s output does not depend only on its intended inputs but also on its context. One contributor to lack of modularity is loading of transcriptional and translational resources, which can induce coupling among otherwise independently-regulated genes. Here, we quantify the effects of resource loading in engineered mammalian genetic systems and develop an endoribonuclease-based feedforward controller that can adapt the expression level of a gene of interest to significant resource loading in mammalian cells. Near-perfect adaptation to resource loads is facilitated by high production and catalytic rates of the endoribonuclease. Our design is portable across cell lines and enables predictable tuning of controller function. Ultimately, our controller is a general-purpose device for predictable, robust, and context-independent control of gene expression. |
| first_indexed | 2024-09-23T17:12:10Z |
| format | Article |
| id | mit-1721.1/133608 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T17:12:10Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1336082023-07-28T20:45:33Z An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells Jones, Ross D Qian, Yili Siciliano, Velia DiAndreth, Breanna Huh, Jin Weiss, Ron Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Synthetic Biology Center Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science © 2020, The Author(s). Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device’s output does not depend only on its intended inputs but also on its context. One contributor to lack of modularity is loading of transcriptional and translational resources, which can induce coupling among otherwise independently-regulated genes. Here, we quantify the effects of resource loading in engineered mammalian genetic systems and develop an endoribonuclease-based feedforward controller that can adapt the expression level of a gene of interest to significant resource loading in mammalian cells. Near-perfect adaptation to resource loads is facilitated by high production and catalytic rates of the endoribonuclease. Our design is portable across cell lines and enables predictable tuning of controller function. Ultimately, our controller is a general-purpose device for predictable, robust, and context-independent control of gene expression. 2021-10-27T19:53:48Z 2021-10-27T19:53:48Z 2020 2021-09-10T18:18:38Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133608 en 10.1038/S41467-020-19126-9 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Jones, Ross D Qian, Yili Siciliano, Velia DiAndreth, Breanna Huh, Jin Weiss, Ron Del Vecchio, Domitilla An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title | An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title_full | An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title_fullStr | An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title_full_unstemmed | An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title_short | An endoribonuclease-based feedforward controller for decoupling resource-limited genetic modules in mammalian cells |
| title_sort | endoribonuclease based feedforward controller for decoupling resource limited genetic modules in mammalian cells |
| url | https://hdl.handle.net/1721.1/133608 |
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