| pubmed-article:17827215 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C0282641 | lld:lifeskim |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C1512977 | lld:lifeskim |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C0042890 | lld:lifeskim |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:17827215 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:17827215 | pubmed:issue | 17 | lld:pubmed |
| pubmed-article:17827215 | pubmed:dateCreated | 2007-9-28 | lld:pubmed |
| pubmed-article:17827215 | pubmed:abstractText | Although adjustable transgene expression systems are considered essential for future therapeutic and biopharmaceutical manufacturing applications, the currently available transcription control modalities all require side-effect-prone inducers such as immunosupressants, hormones and antibiotics for fine-tuning. We have designed a novel mammalian transcription-control system, which is reversibly fine-tuned by non-toxic vitamin H (also referred to as biotin). Ligation of vitamin H, by engineered Escherichia coli biotin ligase (BirA), to a synthetic biotinylation signal fused to the tetracycline-dependent transactivator (tTA), enables heterodimerization of tTA to a streptavidin-linked transrepressor domain (KRAB), thereby abolishing tTA-mediated transactivation of specific target promoters. As heterodimerization of tTA to KRAB is ultimately conditional upon the presence of vitamin H, the system is vitamin H responsive. Transgenic Chinese hamster ovary cells, engineered for vitamin H-responsive gene expression, showed high-level, adjustable and reversible production of a human model glycoprotein in bench-scale culture systems, bioreactor-based biopharmaceutical manufacturing scenarios, and after implantation into mice. The vitamin H-responsive expression systems showed unique band pass filter-like regulation features characterized by high-level expression at low (0-2 nM biotin), maximum repression at intermediate (100-1000 nM biotin), and high-level expression at increased (>100 000 nM biotin) biotin concentrations. Sequential ON-to-OFF-to-ON, ON-to-OFF and OFF-to-ON expression profiles with graded expression transitions can all be achieved by simply increasing the level of a single inducer molecule without exchanging the culture medium. These novel expression characteristics mediated by an FDA-licensed inducer may foster advances in therapeutic cell engineering and manufacturing of difficult-to-produce protein therapeutics. | lld:pubmed |
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| pubmed-article:17827215 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17827215 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17827215 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17827215 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:17827215 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17827215 | pubmed:issn | 1362-4962 | lld:pubmed |
| pubmed-article:17827215 | pubmed:author | pubmed-author:FusseneggerMa... | lld:pubmed |
| pubmed-article:17827215 | pubmed:author | pubmed-author:WeberWilfried... | lld:pubmed |
| pubmed-article:17827215 | pubmed:author | pubmed-author:Daoud-El... | lld:pubmed |
| pubmed-article:17827215 | pubmed:author | pubmed-author:BacchusWillia... | lld:pubmed |
| pubmed-article:17827215 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:17827215 | pubmed:volume | 35 | lld:pubmed |
| pubmed-article:17827215 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17827215 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17827215 | pubmed:pagination | e116 | lld:pubmed |
| pubmed-article:17827215 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
