A tunable dual‐promoter integrator for targeting of cancer cells
Precise discrimination between similar cellular states is essential for autonomous decision‐making scenarios, such as in vivo targeting of diseased cells. Discrimination could be achieved by delivering an effector gene expressed under a highly active context‐specific promoter. Yet, a single‐promoter...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-01-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.99 |
| _version_ | 1797281838234861568 |
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| author | Lior Nissim Roy H Bar‐Ziv |
| author_facet | Lior Nissim Roy H Bar‐Ziv |
| author_sort | Lior Nissim |
| collection | DOAJ |
| description | Precise discrimination between similar cellular states is essential for autonomous decision‐making scenarios, such as in vivo targeting of diseased cells. Discrimination could be achieved by delivering an effector gene expressed under a highly active context‐specific promoter. Yet, a single‐promoter approach has linear response and offers limited control of specificity and efficacy. Here, we constructed a dual‐promoter integrator, which expresses an effector gene only when the combined activity of two internal input promoters is high. A tunable response provides flexibility in choosing promoter inputs and effector gene output. Experiments using one premalignant and four cancer cell lines, over a wide range of promoter activities, revealed a digital‐like response of input amplification following a sharp activation threshold. The response function is cell dependent with its overall magnitude increasing with degree of malignancy. The tunable digital‐like response provides robustness, acts to remove input noise minimizing false‐positive identification of cell states, and improves targeting precision and efficacy. |
| first_indexed | 2024-03-07T17:03:13Z |
| format | Article |
| id | doaj.art-bbbf730e791a4497859a84547be63ac6 |
| institution | Directory Open Access Journal |
| issn | 1744-4292 |
| language | English |
| last_indexed | 2024-03-07T17:03:13Z |
| publishDate | 2010-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj.art-bbbf730e791a4497859a84547be63ac62024-03-03T03:11:50ZengSpringer NatureMolecular Systems Biology1744-42922010-01-0161n/an/a10.1038/msb.2010.99A tunable dual‐promoter integrator for targeting of cancer cellsLior Nissim0Roy H Bar‐Ziv1Department of Materials and Interfaces, The Weizmann Institute of Science Rehovot IsraelDepartment of Materials and Interfaces, The Weizmann Institute of Science Rehovot IsraelPrecise discrimination between similar cellular states is essential for autonomous decision‐making scenarios, such as in vivo targeting of diseased cells. Discrimination could be achieved by delivering an effector gene expressed under a highly active context‐specific promoter. Yet, a single‐promoter approach has linear response and offers limited control of specificity and efficacy. Here, we constructed a dual‐promoter integrator, which expresses an effector gene only when the combined activity of two internal input promoters is high. A tunable response provides flexibility in choosing promoter inputs and effector gene output. Experiments using one premalignant and four cancer cell lines, over a wide range of promoter activities, revealed a digital‐like response of input amplification following a sharp activation threshold. The response function is cell dependent with its overall magnitude increasing with degree of malignancy. The tunable digital‐like response provides robustness, acts to remove input noise minimizing false‐positive identification of cell states, and improves targeting precision and efficacy.https://doi.org/10.1038/msb.2010.99cancergene therapysignal integrationsynthetic biologysystems biology |
| spellingShingle | Lior Nissim Roy H Bar‐Ziv A tunable dual‐promoter integrator for targeting of cancer cells Molecular Systems Biology cancer gene therapy signal integration synthetic biology systems biology |
| title | A tunable dual‐promoter integrator for targeting of cancer cells |
| title_full | A tunable dual‐promoter integrator for targeting of cancer cells |
| title_fullStr | A tunable dual‐promoter integrator for targeting of cancer cells |
| title_full_unstemmed | A tunable dual‐promoter integrator for targeting of cancer cells |
| title_short | A tunable dual‐promoter integrator for targeting of cancer cells |
| title_sort | tunable dual promoter integrator for targeting of cancer cells |
| topic | cancer gene therapy signal integration synthetic biology systems biology |
| url | https://doi.org/10.1038/msb.2010.99 |
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