TF Decoy Technology Development

TF Decoy Technology Development

Recently, transcription factor (TF) decoy technology has been proposed as an effective therapeutic tool against a variety of diseases, including different types of cancer, atherosclerosis, heart failure, abdominal aortic aneurysm and COVID-19[1]. This technology primarily utilizes two types of decoys: decoy oligodeoxynucleotides (ODNs) and decoy peptides. Alfa Chemistry is passionate about researching the use of TF decoy technology in the treatment of disease. If you are also interested in this field, please contact us.

Mechanism of Action

Mechanism of action of decoy ODNs

ODNs are short double-stranded deoxyribonucleic acid (DNA) that have a similar sequence to the DNA-binding site of TFs and can selectively block TF activation of target genes (Figure 1; left)[2]. By competing with trans elements in target genes' regulatory regions, Decoy ODNs inhibit gene transcription at the transcriptional level. In recent years, decoy ODNs have been used as a therapeutic tool for a variety of diseases, including cancer.

Mechanism of action of decoy peptides

Decoy peptides (or decoy receptors) are "sticky" proteins similar to functional receptors on cytokines and chemokines. They can attract certain ligands such as inflammatory cytokines, and compete with target receptors although decoy peptides do not initiate signaling (Figure 1; right)[2]. Decoy peptides are designed to trap specific ligand molecules as efficiently as their respective receptors. Therefore, ligand binding to the functional receptor is inhibited and the corresponding signaling pathway is suppressed.

The figure describes in detail the mechanism of action of decoy ODNs (left) and decoy peptides (right).Figure 1. The mechanism of action of decoy ODNs (left) and decoy peptides (right). Left: (A) Without decoy ODNs: normal transcription of target genes. (B) In the presence of decoy ODNs: decoy ODNs bind to a specific transcription factor. Right: (A) Normal cells without decoy peptides. (B) Decoy peptides act as molecular traps and bind to specific ligands.

Applications of TF Decoy Technology

Initially, skin conditions such as atopic dermatitis were best suited for the use of TF decoy technology. Subsequent studies have shown that TF decoy technology may have therapeutic value for cancer, organ transplantation, asthma, and cardiovascular diseases. Recently, the therapeutic effects of decoy molecules on a number of other indications have been published, examples of which are given below[3].

a) Rheumatoid arthritis (NF-jB TF decoy ODNs coated with polysaccharide- based nanoparticles).
b) Alzheimer's disease (TF decoy ODNs interfere with calcineurin-FOXO3 interaction).
c) Limited range of motion (ROM) as a result of joint contracture (ribbon-type hypoxia inducible factor-1 TF decoy ODNs).
d) Prevention of acute and chronic post-surgical pain (intrathecal administration of an early growth response protein-1 TF decoy).

Our Development Process

Alfa Chemistry provides TF decoy technology development services, and the following is our main development process.

No matter which stage of TF decoy technology development you encounter challenges, we will provide you with timely help.

  • Target selection.
  • Sequence design of decoys.
  • Synthesis and chemical modification of decoys.
  • Purification and analysis of decoys.
  • Delivery system selection or development of decoys.
  • Nonclinical evaluation of decoys.
  • Scale-up of decoys.

References

  1. Mahjoubin-Tehran, M.; et al. Decoys as potential therapeutic tools for diabetes. Drug Discovery Today. 2021, 6: 1669.
  2. Mahjoubin-Tehran, M.; et al. Decoy technology as a promising therapeutic tool for atherosclerosis. International Journal of Molecular Sciences. 2021, 22: 4420.
  3. Hecker, M.; Wagner, A.H. Transcription factor decoy technology: a therapeutic update. Biochemical Pharmacology. 2017, 15(144): 29-34.

Our products and services are for research use only and cannot be used for any clinical purposes.

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