The "Gene Switch" technology does not involve "polymers, peptides, and lipids". That reference is to some of Gene Medicines gene delivery systems. I did some research on the matter and came up with the following information. I can't claim to understand this stuff and would appreciate it if a more knowledgeble poster would comment.
John de C
Here are some links to Gene Switch press Releases:
GeneMedicine Announces Demonstration of Negative GeneSwitch™ - Researchers make further advancements in regulation of gene expression. THE WOODLANDS, TX, May 5, 1997
gmed.com
GeneMedicine Announces Successful in vivo Demonstration of Tissue-Specific GeneSwitch™ Technology, THE WOODLANDS, TX, March 17, 1997
gmed.com
Here are some of the publications:
ncbi.nlm.nih.gov
Nat Biotechnol 1997 Mar;15(3):239-43
Ligand-inducible and liver-specific target gene expression in transgenic mice. Wang Y, DeMayo FJ, Tsai SY, O'Malley BW Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Transgenic mice have been used as models for tissue-specific gene regulation and to examine the molecular and cellular effects of altered expression of specific gene in disease processes such as tumorigenesis. Because of the deleterious effects of constitutive expression of transgenes, which frequently result in prenatal or postnatal death, only a limited number of disease models have been established in transgenic mice. We report an inducible binary transactivation system that permits the control of transgene expression in a tissue-specific and inducible fashion in mice. In this system, transcription of the target transgene is kept silent until turned on by the administration of an exogenous compound. We also demonstrate that expression level of the
target gene can be induced three to four orders of magnitude and can be controlled by the administrated compound in a dose-dependent manner.
ncbi.nlm.nih.gov
Front Biosci 1998 Jan 1;3:c1-7
A regulatory system for target gene expression. Burcin MM, O Malley BW, Tsai SY
Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Temporally-regulated expression of endogenous genes is a desirable goal in stable cell line and transgenic animal systems, as well as in clinical gene therapy. Protocols for introducing genes into stable cell lines and experimental animals are often unsatisfactory due to the constitutive expression of such transgenes. To circumvent this problem we have demonstrated specific and temporally regulable expression of a target gene in vivo effected by a chimeric regulator in response to an orally-administered, non-toxic chemical. This regulatory system utilizes a chimeric regulator GLVP, consisting of a mutated human progesterone receptor ligand binding domain (PRLBD-delta) fused to the yeast GAL4 DNA binding domain (DBD) and the HSV VP16 transcriptional activation domain and whose activity is solely regulable by non-physiological doses of RU486 but not by progesterone or other endogenous progestins. Replacing the activation domain of the chimeric regulator with a transcriptional repression domain results in inducible repression of target gene expression in vitro. Our regulatory system
functions in transient and stable transfections as well as in transgenic animals, and will have a wide variety of potential applications.
ncbi.nlm.nih.gov
Gene Ther 1997 May;4(5):432-41
Positive and negative regulation of gene expression in eukaryotic cells with an inducible transcriptional regulator. Wang Y, Xu J, Pierson T, O'Malley BW, Tsai SY
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
To facilitate the understanding of the complex process of target gene expression and its control, we report a modified inducible system for activation or repression of target gene expression in response to an exogenously administered compound. The main component of this inducible system is a chimeric transcriptional activator (GLVP) consisting of an N-terminal VP16 transcriptional activation domain fused to a yeast GAL4 DNA binding domain and a mutated human progesterone receptor (hPR) ligand binding domain (LBD). This chimeric regulator binds to a target gene containing the 17-mer GAL4 upstream activation sequence (UAS) in the presence of anti-progesterone, RU486. We showed that the combination of two different types of domains (VP16 and poly-glutamine stretch) into one chimeric molecule could result in a further increase in transcriptional activation potency. Through mutational analysis, we modified the original GLVP and generated a more potent version of the RU486 inducible regulator GL914 VPc with a 19 amino acid deletion of the hPR-LBD (delta C19) and a C-terminally located VP16 activation domain. More importantly, this new chimeric regulator can effectively activate target gene expression at a much lower concentration of RU486 (0.01 nM). The concept of RU486 regulatable gene expression is not limited to gene activation. By replacing the VP16 activation domain with a KRAB transcriptional repression domain, we are able to achieve inducible repression of target gene expression. We also present evidence that individual functional domains within a chimeric protein could modulate each other's function depending on their relative positions within the molecule. Using this potent regulator, we demonstrate that inducible nerve growth factor (NGF) secretion into conditioned media can elicit neurite outgrowth in co-cultured PC12 cells. This new versatile inducible system can potentially be used to control target gene expression in a mammalian system in vivo.
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