期刊
JOURNAL OF COMPUTATIONAL BIOLOGY
卷 18, 期 2, 页码 195-203出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/cmb.2010.0208
关键词
computational biology; synthetic gene networks; synthetic biology; shRNA; aptamers
类别
资金
- Telethon [TGM06E01] Funding Source: Medline
We constructed and modeled a novel synthetic network which may be able to exhibit bistable expression of a reporter gene in mammalian cells. This network is based on an aptamer-fused short-hairpin RNA (shRNA) directed against a single mRNA encoding both a EGFP reporter gene and the repressor tTR-KRAB, which, in turn, represses transcription of the shRNA. The activity of the shRNA can be controlled by an inducer molecule (theophylline) which prevents the aptamer-fused shRNA to be properly processed. Repression of the tTR-KRAB can be relieved by treatment with doxycyline. This reciprocal negative feedback loop can exhibit a bistable response, as shown through the mathematical analysis performed here. Specifically, the network can be controlled to induce sustained expression of a shRNA, or the reporter gene, with a transient input of two different inducer molecules.
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