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Despite the expanding library of genetic parts, construction of integrated synthetic circuits with desired specifications remains challenging in part due to intricate dependence on sequence contexts, where unexpected narrow dynamic ranges and leaky expression can plague system performance. To provide an alternative approach to the screening process of iterative design\u2010build\u2010test cycles,\n                    <jats:bold>SUPER<\/jats:bold>\n                    (\n                    <jats:bold>\n                      <jats:styled-content>S<\/jats:styled-content>\n                    <\/jats:bold>\n                    ynthetic\n                    <jats:bold>\n                      <jats:styled-content>U<\/jats:styled-content>\n                    <\/jats:bold>\n                    pcycling\n                    <jats:bold>\n                      <jats:styled-content>P<\/jats:styled-content>\n                    <\/jats:bold>\n                    latform for\n                    <jats:bold>\n                      <jats:styled-content>E<\/jats:styled-content>\n                    <\/jats:bold>\n                    ngineering\n                    <jats:bold>\n                      <jats:styled-content>R<\/jats:styled-content>\n                    <\/jats:bold>\n                    egulators), a modular platform for upcycling genetic devices is introduced. Inspired by antagonistic regulation mechanisms, SUPER employs small RNA as an add\u2010on controller to modulate gene expression patterns without genetic modification of target regulators. SUPER not only enhances the performance of RNA\u2010, chemical\u2010, temperature\u2010, and protein\u2010responsive regulators up to 1011%, but also allows to cover an expanded dynamic range up to 22\u00a0018.9\u2010fold. This enhanced control can provide genetic circuit stability, particularly under strong selective pressures, as demonstrated with a Holin\u2010expressing kill switch integrated with SUPER, maintaining stable functionality for over 30 days. Finally, SUPER combines with an environmental sensor, TlpA36, functioning as a chemical\u2010 and temperature\u2010responsive 2\u2010input kill switch. Featuring straightforward design, minimal cellular burden, and expanded tunability, SUPER provides a systematic upcycling framework for genetic circuit construction in biotechnology.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514653","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T03:56:16Z","timestamp":1765857376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SUPER: Upcycling Genetic Parts for Precise Gene Expression Control, Leakage Minimization, and Genetic Circuit Stability"],"prefix":"10.1002","volume":"13","author":[{"given":"Taeyang","family":"Heo","sequence":"first","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology Pohang 37673 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongwon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology Pohang 37673 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woosub","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology Pohang 37673 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-1006","authenticated-orcid":false,"given":"Jongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology Pohang 37673 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"49","volume":"78","author":"Rawls R. 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