Related Experiment Video
Updated: Jun 23, 2026
11:27
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Inflammatory cell-specific transgene expression system responding to Ikappa-B kinase beta activation
Daisuke Asai1, Akira Tsuchiya, Jeong-Hun Kang
1Department of Microbiology, St Marianna University School of Medicine, Kawasaki, Japan. asai@marianna-u.ac.jp
The Journal of Gene Medicine
|May 9, 2009
Summary
This study introduces a novel gene delivery system that responds to cellular signals, specifically targeting inflammatory cells. The system successfully triggered gene expression in response to inflammation, offering a new approach for targeted gene therapy.
Area of Science:
- Biotechnology
- Molecular Biology
- Gene Therapy
Background:
- Controlling inflammation is crucial for managing numerous human diseases.
- Existing strategies for converting intracellular signals into gene expression for cellular normalization are limited.
- A novel drug or gene delivery system responding to cellular signals (D-RECS) was previously proposed.
Purpose of the Study:
- To apply the D-RECS concept to inflammatory cells.
- To utilize Ikappa-B kinase (IKK) as a trigger for gene expression in inflammatory cells.
Main Methods:
- Synthesis and reactivity assessment of cationic IKKbeta substrates.
- Preparation of IKKbeta-responsive polymers and subsequent formation of polymer/DNA complexes (polyplexes).
- Evaluation of polyplex behavior with IKKbeta and assessment of transgene expression in living cells under NF-kappaB activation.
Main Results:
- Synthesized peptides and prepared polymers/polyplexes were phosphorylated by IKKbeta.
- IKKbeta induced polyplex disintegration and release of free DNA.
- Transgene expression was achieved in inflammatory cells stimulated with a pro-inflammatory stimulus.
Conclusions:
- The D-RECS concept was successfully demonstrated for cell-specific gene expression in inflammatory cells.
- This approach offers a potential strategy for targeted gene therapy in inflammatory conditions.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:16TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...