{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:25:09Z","timestamp":1788906309857,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of China","award":["2023YFF1204500"],"award-info":[{"award-number":["2023YFF1204500"]}]},{"name":"Ministry of Science and Technology of China","award":["2020YFA0906900"],"award-info":[{"award-number":["2020YFA0906900"]}]},{"name":"Ministry of Science and Technology of China","award":["2021YFF1200500"],"award-info":[{"award-number":["2021YFF1200500"]}]},{"name":"Ministry of Science and Technology of China","award":["2020YFA0907101"],"award-info":[{"award-number":["2020YFA0907101"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62250007"],"award-info":[{"award-number":["62250007"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62225307"],"award-info":[{"award-number":["62225307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071412"],"award-info":[{"award-number":["32071412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAS Youth Interdisciplinary Team"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Precise control of gene activity within a host cell is crucial in bioengineering applications. Despite significant advancements in cis-regulatory sequence activity prediction and reverse engineering, the context-dependent effects of host cellular environment have long been neglected, leading to ongoing challenges in accurately modeling regulatory processes. Here, we introduce an insulated design strategy to purify and model host-independent transcriptional activity. By integrating heterologous paired cis- and trans-regulatory modules into an orthogonal host cell, we established a controllable transcriptional regulatory system. Using a deep learning-based algorithm combined with an experimental data purification process, we achieved the de novo design full-length transcriptional promoter sequences driven by a host-independent activity landscape. Notably, this landscape accurately captured the transcriptional activity of the insulated system, enabling the generation of cis-regulatory sequences with desirable sequence and functional diversity for two distinct trans-RNA polymerases. Importantly, their activities are precisely predictable in both bacterial (Escherichia coli) and mammalian (Chinese hamster ovary) cell lines. We anticipated that de novo design strategy can be expanded to other complex cis-regulatory elements by integrating the deep learning-based algorithm with the construction of paired cis- and trans-regulatory modules in orthogonal host systems.<\/jats:p>","DOI":"10.1093\/nar\/gkaf611","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T12:27:57Z","timestamp":1751632077000},"source":"Crossref","is-referenced-by-count":7,"title":["<i>De novo<\/i> design of insulated <i>cis<\/i>-regulatory elements based on deep learning-predicted fitness landscape"],"prefix":"10.1093","volume":"53","author":[{"given":"Haochen","family":"Wang","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division , Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing 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Synthetic and Systems Biology; Bioinformatics Division , Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing 100084,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-6038","authenticated-orcid":false,"given":"Chunbo","family":"Lou","sequence":"additional","affiliation":[{"name":"Center for Cell and Gene Circuit Design, State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"2025070408275069900_B1","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/s41576-020-0258-4","article-title":"mRNAs, proteins and the emerging principles of gene expression 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