Useful Links

Gene Activation by Hairpinning

Researchers have made Molecular Lock control systems with components described in patents issued to The Gene Pool, Inc. and have confirmed the ability of Molecular Locks to selectively turn on synthetic promoters by hairpinning a nucleic acid. This paper shows how cooperative binding of Molecular Locks produces efficient, selective activation of test promoters. cI hybrids, such as the ones studied by Langdon et al., 2001, is described by the Weininger patent (U.S. #5,871,902).

• Langdon RC, Burr T, Pagan-Westphal S, Hochschild A. “A chimeric activator of transcription that uses two DNA-binding domains to make simultaneous contact with pairs of recognition sites.” Mol Microbiol. 2001 Aug;41(4):885-96.
  
  
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Cooperative assembly of proteins controls gene expression in Lambda phage. Cooperative assembly of cI monomers onto bacteriophage lambda operator sites OR1 and OR2 in the right promoter utilizes cI C-terminal domains that octomerize. The N terminal domain of cI on OR2 tightens the binding of RNA polymerase holoenzyme complex to the right promoter stimulating further cI transcription.

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  Zurla C, Manzo C, Dunlap D, Lewis DE, Adhya S, Finzi L. “Direct demonstration and quantification of long-range DNA looping by the lambda bacteriophage repressor.” Nucleic Acids Res. 2009 May;37(9):2789-95. Epub 2009 Mar 10
  
  
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  Dodd IB, Perkins AJ, Tsemitsidis D, Egan JB. “Octamerization of lambda CI repressor is needed for effective repression of P(RM) and efficient switching from lysogeny.” Genes Dev. 2001 Nov 15;15(22):3013-22
  
  

Stem Cell Differentiation by the Delivery or Reduction of Cellular Transcription Factors

Transcription factors can induce differentiation of stem cells by shifting the equilibrium of the association of transcription factors that activate DNA. Unlike Molecular Locks, an increase or decrease in transcription factors may have an influence on pathways are not targeted.

• Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. “Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.” Cell. 2010 Aug 6;142(3):375-86.
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  Gretchen Vogel. “Turning Scar Tissue Into a Beating Heart” ScienceNOW, American Association for the Advancement of Science., Aug 2010 < http://news.sciencemag.org/sciencenow/2010/08/turning-scar-tissue-into-a-beati.html >
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  Von Salisch S, Klar M, Thurisch B, Bungert J, Dame C. “Gata4 and Sp1 regulate expression of the erythropoietin receptor in cardiomyocytes.” J Cell Mol Med., 2010 Oct 3. doi: 10.1111/j.1582-4934.2010.01193.x.

Cellular Delivery Domains

Molecular Locks can be targeted to specific cells by attaching Molecular Lock components to delivery domains in order to deliver the Molecular Lock components to specific cells (e.g., substance P) or all cells in general (e.g., diphtheria toxin delivery components).

• Moskaug JO, Stenmark H, Sandvig K, Olsnes S. “Translocation of diphtheria toxin to the cytosol and formation of cation selective channels.” J Physiol (Paris) 1990;84(3):191-6.
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  Rizk SS, Luchniak A, Uysal S, Brawley CM, Rock RS, Kossiakoff AA. “An engineered substance P variant for receptor-mediated delivery of synthetic antibodies into tumor cells.” Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11011-5. Epub 2009 Jun 22
  
  
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  Zakrzewska M , Zhen Y , Wiedlocha A , Olsnes S , Wesche J. “Size-limitation in translocation of FGF1 fusion proteins across the endosomal membrane.” Biochemistry 2009 Aug 4;48(30):7209-18