A regulatory system for use in gene transfer.

Abstract

We recently have demonstrated that a C-terminal deletion mutant

Doxycycline-regulated lentiviral vector system with a novel reverse transactivator rtTA2S-M2 shows a tight control of gene expression in vitro and in vivo

“…3,[25][26][27][28] Some major advantages of the Tet-on system compared to the other gene regulation systems are a well-known safety profile, easy availability and good tissue penetration of the regulating drug dox. Bacterial origin of the Tet-on elements assures minimal interference with endogenous physiological processes of the eukaryotic cells.…”

Prolonged and inducible transgene expression in the liver using gutless adenovirus: A potential therapy for liver cancer

“…[41][42][43] They all involve the drugdependent recruitment of a transcriptional activation domain to a basal promoter driving the gene of interest but differ in the mechanism of recruitment. [41][42][43][44][45] In the mifepristone system, drug-regulated transcription is achieved by fusing a heterologous DNA-binding domain of yeast GAL4 protein and activation domain of VP-16 or NF-B p65 proteins to a mutant human progesterone receptor that is unaffected by endogenous hormones but is activated by synthetic antiprogestins at doses sufficiently low to avoid side-effects in human. 45,46 The properties of the mifepristone-regulated system have been investigated in transgenic animals and naked DNA plasmid in muscles.…”

“…[41][42][43][44][45] In the mifepristone system, drug-regulated transcription is achieved by fusing a heterologous DNA-binding domain of yeast GAL4 protein and activation domain of VP-16 or NF-B p65 proteins to a mutant human progesterone receptor that is unaffected by endogenous hormones but is activated by synthetic antiprogestins at doses sufficiently low to avoid side-effects in human. 45,46 The properties of the mifepristone-regulated system have been investigated in transgenic animals and naked DNA plasmid in muscles. [47][48][49][50] Burcin et al 45 have incorporated this system into a gutless adenovirus with a human growth hormone target gene.…”

“…45,46 The properties of the mifepristone-regulated system have been investigated in transgenic animals and naked DNA plasmid in muscles. [47][48][49][50] Burcin et al 45 have incorporated this system into a gutless adenovirus with a human growth hormone target gene. They showed that background transcription was undetectable in vitro and in vivo and that over 50 days' human growth hormone production could be cycled on and off 3 times or maintained at steady state levels by delivery of the inducer.…”

Double‐inducible gene activation system for caspase 3 and 9 in epidermis

“…While current inducible systems, such as RU486 and chemical inducers of dimerization (CID), have improved earlier inducible models (Gossen et al, 1995) (Wang et al, 1994), no single system is perfect at present. One potential drawback of these systems is leakage of transgene expression, causing limitations of each system.…”