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Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation

[Image: see text] Synthetic mRNA circuits manipulate cell fate by controlling output protein expression via cell-specific input molecule detection. Most current circuits either repress or enhance output production upon input binding. Such binary input–output mechanisms restrict the fine-tuning of pr...

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Autores principales: Tan, Kaixin, Hu, Yaxin, Liang, Zhenghua, Li, Cheuk Yin, Yau, Wai Laam, Kuang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510700/
https://www.ncbi.nlm.nih.gov/pubmed/37652441
http://dx.doi.org/10.1021/acssynbio.3c00144
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author Tan, Kaixin
Hu, Yaxin
Liang, Zhenghua
Li, Cheuk Yin
Yau, Wai Laam
Kuang, Yi
author_facet Tan, Kaixin
Hu, Yaxin
Liang, Zhenghua
Li, Cheuk Yin
Yau, Wai Laam
Kuang, Yi
author_sort Tan, Kaixin
collection PubMed
description [Image: see text] Synthetic mRNA circuits manipulate cell fate by controlling output protein expression via cell-specific input molecule detection. Most current circuits either repress or enhance output production upon input binding. Such binary input–output mechanisms restrict the fine-tuning of protein expression to control complex cellular events. Here we designed mRNA circuits using enhancer/repressor modules that were independently controlled by different input molecules, resulting in bidirectional output regulation; the maximal enhancement over maximal repression was 57 fold. The circuit either enhances or represses protein production in different cells based on the difference in the expression of two microRNAs. This study examined novel bidirectional circuit designs capable of fine-tuning protein production by sensing multiple input molecules. It also broadened the scope of cell manipulation by synthetic mRNA circuits, facilitating the development of mRNA circuits for precise cell manipulation and providing cell-based solutions to biomedical problems.
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spelling pubmed-105107002023-09-21 Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation Tan, Kaixin Hu, Yaxin Liang, Zhenghua Li, Cheuk Yin Yau, Wai Laam Kuang, Yi ACS Synth Biol [Image: see text] Synthetic mRNA circuits manipulate cell fate by controlling output protein expression via cell-specific input molecule detection. Most current circuits either repress or enhance output production upon input binding. Such binary input–output mechanisms restrict the fine-tuning of protein expression to control complex cellular events. Here we designed mRNA circuits using enhancer/repressor modules that were independently controlled by different input molecules, resulting in bidirectional output regulation; the maximal enhancement over maximal repression was 57 fold. The circuit either enhances or represses protein production in different cells based on the difference in the expression of two microRNAs. This study examined novel bidirectional circuit designs capable of fine-tuning protein production by sensing multiple input molecules. It also broadened the scope of cell manipulation by synthetic mRNA circuits, facilitating the development of mRNA circuits for precise cell manipulation and providing cell-based solutions to biomedical problems. American Chemical Society 2023-08-31 /pmc/articles/PMC10510700/ /pubmed/37652441 http://dx.doi.org/10.1021/acssynbio.3c00144 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Tan, Kaixin
Hu, Yaxin
Liang, Zhenghua
Li, Cheuk Yin
Yau, Wai Laam
Kuang, Yi
Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title_full Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title_fullStr Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title_full_unstemmed Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title_short Dual Input-Controlled Synthetic mRNA Circuit for Bidirectional Protein Expression Regulation
title_sort dual input-controlled synthetic mrna circuit for bidirectional protein expression regulation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10510700/
https://www.ncbi.nlm.nih.gov/pubmed/37652441
http://dx.doi.org/10.1021/acssynbio.3c00144
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