{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T11:43:15Z","timestamp":1764675795707,"version":"3.46.0"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T00:00:00Z","timestamp":1157414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2006,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    RNAi has been useful in the study of biochemical pathways, but has not been widely used as a tool in metabolic engineering. The work described here makes use of double\u2010stranded RNA (dsRNA) for the post\u2010transcriptional gene silencing of\n                    <jats:italic>TSC1<\/jats:italic>\n                    in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    S2 cells.\n                    <jats:italic>TSC1<\/jats:italic>\n                    downregulates the insulin\u2010mediated signal transduction pathway, and serves as a metabolic control to guard against cellular overproliferation and tumorogenesis in both flies and mammals. By silencing\n                    <jats:italic>TSC1<\/jats:italic>\n                    with in vitro\u2010synthesized dsRNA, we have created a tunable and specific metabolic \u201cthrottle\u201d that, like insulin, apparently increases the specific growth rate of S2 cells in a dose\u2010dependent manner. This \u201cthrottle,\u201d augments the benefits of insulin addition while apparently avoiding deleterious and pleiotropic effects which can lead to lysis. During the period wherein dsRNA was active, cell growth rate was increased by 11% by the addition of 15 \u00b5g\/mL dsTSC1 and by over 20% by the addition of 30 \u00b5g\/mL dsTSC1. Additionally, synthesis of recombinant green fluorescent protein (GFP) was increased nearly 50% in a stable S2 cell line inducibly expressing GFP. Accordingly, we have \u201ctuned\u201d a normally tumorogenic pathway in animals into an advantage for both growth and recombinant product synthesis in cell culture. Potential applications for improving eukaryotic cell culture are anticipated. \u00a9 2006 Wiley Periodicals, Inc.\n                  <\/jats:p>","DOI":"10.1002\/bit.20951","type":"journal-article","created":{"date-parts":[[2006,9,5]],"date-time":"2006-09-05T21:21:25Z","timestamp":1157491285000},"page":"645-652","source":"Crossref","is-referenced-by-count":11,"title":["Engineering eukaryotic signal transduction with RNAi: Enhancing\n                    <i>Drosophila<\/i>\n                    S2 cell growth and recombinant protein synthesis via silencing of\n                    <i>TSC1<\/i>"],"prefix":"10.1002","volume":"95","author":[{"given":"John C.","family":"March","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William 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