Abstract:
:Applications of conditional gene expression, whether for therapeutic or basic research purposes, are increasingly requiring mammalian gene control systems that exhibit far tighter control properties. While numerous approaches have been used to improve the widely used Tet-regulatory system, many applications, particularly with respect to the engineering of synthetic gene networks, will require a broader range of tightly performing gene control systems. Here, a generically applicable approach is described that utilizes intronically encoded siRNA on the relevant transregulator construct, and siRNA sequence-specific tags on the reporter construct, to minimize basal gene activity in the off-state of a range of common gene control systems. To demonstrate tight control of residual expression the approach was successfully used to conditionally express the toxic proteins RipDD and Linamarase. The intronic siRNA concept was also extended to create a new generation of compact, single-vector, autoinducible siRNA vectors. Finally, using improved regulation systems a mammalian epigenetic toggle switch was engineered that exhibited superior in vitro and in vivo induction characteristics in mice compared to the equivalent non-intronic system.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Greber D,El-Baba MD,Fussenegger Mdoi
10.1093/nar/gkn443subject
Has Abstractpub_date
2008-09-01 00:00:00pages
e101issue
16eissn
0305-1048issn
1362-4962pii
gkn443journal_volume
36pub_type
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.9.2295
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz553
更新日期:2019-09-05 00:00:00
abstract::Analysis of the human protein-tyrosine phosphatase (PTP) PTPRJ mRNA detected three in-frame AUGs at the 5'-end (starting at nt +14, +191 and +356) with no intervening stop codons. This tandem AUG arrangement is conserved between humans and the mouse and is unique among the genes of the classical PTPs. Until now it was...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn391
更新日期:2008-08-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh628
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.24.6805
更新日期:1991-12-25 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/12.1part1.281
更新日期:1984-01-11 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh803
更新日期:2004-09-08 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2016-01-08 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2017-01-04 00:00:00
abstract::Infrared and UV spectroscopies have been used to study the assembly of a hairpin nucleotide sequence (nucleotides 3-30) of the 5' non-coding region of the hepatitis C virus RNA (5'-GGCGGGGAUUAUCCCCGCUGUGAGGCGG-3') with a RNA 20mer ligand (5'-CCGCCUCACAAAGGUGGGGU-3') in the presence of magnesium ion and spermidine. The...
journal_title:Nucleic acids research
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abstract::Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the Notch1 intracellular domain (NICD1), a hallmark of the leukemogenic proce...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1989-03-11 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkm521
更新日期:2007-01-01 00:00:00
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journal_title:Nucleic acids research
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更新日期:1994-12-11 00:00:00