Reprogramming a Doxycycline-Inducible Gene Switch System for Bacteria-Mediated Cancer Therapy
© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society..
PURPOSE: Attenuated Salmonella typhimurium is a potential biotherapeutic antitumor agent because it can colonize tumors and inhibit their growth. The present study aimed to develop a doxycycline (Doxy)-inducible gene switch system in attenuated S. typhimurium and assess its therapeutic efficacy in various tumor-bearing mice models.
PROCEDURES: A Doxy-inducible gene switch system comprising two plasmids was engineered to trigger the expression of cargo genes (Rluc8 and clyA). Attenuated S. typhimurium carrying Rluc8 were injected intravenously into BALB/c mice bearing CT26 tumors, and bioluminescence images were captured at specified intervals post-administration of doxycycline. The tumor-suppressive effects of bacteria carrying clyA were evaluated in BALB/c mice bearing CT26 tumors and in C57BL/6 mice bearing MC38 tumors.
RESULTS: Expression of the fimE gene, induced only in the presence of Doxy, triggered a unidirectional switch of the POXB20 promoter to induce expression of the cargo genes. The switch event was maintained over a long period of bacterial culture. After intravenous injection of transformed Salmonella into mice bearing CT26 tumors, the bacteria transformed with the Doxy-inducible gene switch system for Rluc8 targeted only tumor tissues and expressed the payloads 2 days after Doxy treatment. Notably, bacteria carrying the Doxy-inducible gene switch system for clyA effectively suppressed tumor growth and prolonged survival, even after just one Doxy induction.
CONCLUSIONS: These results suggest that attenuated S. typhimurium carrying this novel gene switch system elicited significant therapeutic effects through a single induction triggering and were a potential biotherapeutic agent for tumor therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Molecular imaging and biology - 26(2024), 1 vom: 29. Feb., Seite 148-161 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ngo, Hien Thi-Thu [VerfasserIn] |
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| Links: |
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| Themen: |
DNA recombinase |
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| Anmerkungen: |
Date Completed 01.02.2024 Date Revised 01.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s11307-023-01879-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © 2023. The Author(s), under exclusive licence to World Molecular Imaging Society. | ||
| 520 | |a PURPOSE: Attenuated Salmonella typhimurium is a potential biotherapeutic antitumor agent because it can colonize tumors and inhibit their growth. The present study aimed to develop a doxycycline (Doxy)-inducible gene switch system in attenuated S. typhimurium and assess its therapeutic efficacy in various tumor-bearing mice models | ||
| 520 | |a PROCEDURES: A Doxy-inducible gene switch system comprising two plasmids was engineered to trigger the expression of cargo genes (Rluc8 and clyA). Attenuated S. typhimurium carrying Rluc8 were injected intravenously into BALB/c mice bearing CT26 tumors, and bioluminescence images were captured at specified intervals post-administration of doxycycline. The tumor-suppressive effects of bacteria carrying clyA were evaluated in BALB/c mice bearing CT26 tumors and in C57BL/6 mice bearing MC38 tumors | ||
| 520 | |a RESULTS: Expression of the fimE gene, induced only in the presence of Doxy, triggered a unidirectional switch of the POXB20 promoter to induce expression of the cargo genes. The switch event was maintained over a long period of bacterial culture. After intravenous injection of transformed Salmonella into mice bearing CT26 tumors, the bacteria transformed with the Doxy-inducible gene switch system for Rluc8 targeted only tumor tissues and expressed the payloads 2 days after Doxy treatment. Notably, bacteria carrying the Doxy-inducible gene switch system for clyA effectively suppressed tumor growth and prolonged survival, even after just one Doxy induction | ||
| 520 | |a CONCLUSIONS: These results suggest that attenuated S. typhimurium carrying this novel gene switch system elicited significant therapeutic effects through a single induction triggering and were a potential biotherapeutic agent for tumor therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DNA recombinase | |
| 650 | 4 | |a Doxycycline-inducible gene switch | |
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| 700 | 1 | |a You, Sung-Hwan |e verfasserin |4 aut | |
| 700 | 1 | |a Van Nguyen, Khuynh |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, So-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Yeongjin |e verfasserin |4 aut | |
| 700 | 1 | |a Min, Jung-Joon |e verfasserin |4 aut | |
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