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Design and Chemical Modification of Decoy

Transcription factor is the key to target gene regulation. In the transcriptional initiation stage, transcription factors combine with cis-elements to activate the transcriptional expression of target genes. Different transcription factor acts on different DNA sequences and regulates the expression of different genes. The same transcription factor can regulate the expression of multiple genes. Transcription factor (decoy) strategy is a gene therapy and regulation approach. The decoy strategy of transcription factors is to synthesize double-stranded oligodeoxynucleotides (dsODNs) with high affinity consistent with cis-elements to transfect cells. The dsODNs competition inhibits the binding of ttranscription factor with cis-element, and interferes with DNA binding activity of transcription factor, thus inhibits the expression of endogenous target gene. Decoy nucleic acid drug targeting transcription factors regulates gene expression at the transcriptional level so as to achieve the therapeutic purpose. Decoy nucleic acid drug is a gene transcriptional regulation drug.

Creative Biolabs offers solutions for the discovery of nucleic acid drugs, including design and chemical modification of decoy. Using advanced in vitro, in vivo, molecular biology and analytical chemistry methods, Creative Biolabs helps customers accelerate the process of nucleic acid drug discovery.

Our Decoy Service:

Creative Biolabs provides decoy design and chemical modification services. The constructed decoy strategy can be used for further drug development research.

  • Chemical Modifications of Decoy. Early decoy oligonucleotides are designed as double-stranded linear nucleotides. They face the disadvantages of poor intracellular stability, intolerance to the role of RNase H and induction of immune response. Creative Biolabs can optimize the structure by chemical modification to solve these shortcomings.
    • In order to enhance the intracellular stability of the cells, the synthetic products can be chemically modified with thiophosphorylation and methyl phosphorylation, but they could not tolerate the effect of RNase H and may induce immune reaction.
    • By synthesizing dumbbell-shaped circulating double-stranded nucleotides and covalently modifying to link two complementary nucleotide chains, the synthetic products can better tolerate RNAase H and effectively transfect into cells
    • Creative Biolabs can provide locked nucleic acids (LNA), peptide nucleic acids (PNA) and palindromic structures of decoy to improve transfection efficiency and stability.
  • Decoy Strategy of Transcription Factor: Creative Biolabs provides customers with a variety of personalized solutions of decoy strategy.
    • E2F decoy. E2F decoy and binding specifically to the transcription factor E2F, multiple cell cycle genes can be inhibited to interfere cell proliferation.
    • NF - kappaB decoy. NF- kappaB decoy is a transcription factor that exists in almost all cells, affecting a variety of cytokines such as IL-1, IL-2, IL-6, IL-8, TNF-a and adhesion molecules ICAM-1 and VCAM-1, which is widely involved in the body's defense response, tissue damage and stress, cell differentiation and apoptosis.
    • AP-1 decoy. AP-1 decoy is a dimer transcription factor composed of Fos and Jun or activated transcription factor subunits that can bind to AP-1 DNA binding sites. AP-1 regulates the expression of IL-2, TGF - β and collagenase. Its activity is closely related to cell proliferation.
    • STAT3 decoy. STAT3 decoy is an important member of the signal transducers and activators of transcription (STATs). After stimulated by extracellular signals such as growth factors, cytokines and hormones, STAT signaling pathway regulates the transcription of specific target genes in the nucleus and affects cell proliferation, differentiation and apoptosis.

References

  1. Papavassiliou KA, et al. Transcription Factor Drug Targets. J Cell Biochem. 2016, 117(12):2693-2696.
  2. Ghosh D, et al. Transcription factor therapeutics: long-shot or lodestone. Curr Med Chem. 2005, 12(6):691-701.

*For Research Use Only. Not for use in diagnostic procedures.

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