RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis
- Title
- RNA interference-mediated suppression of TNF-α converting enzyme as an alternative anti-TNF-α therapy for rheumatoid arthritis
- Author
- 양철수
- Keywords
- Gene therapy; Human primary synovial cells and osteoclast precursor; Rheumatoid arthritis; TNF-α converting enzyme
- Issue Date
- 2021-02
- Publisher
- Elsevier BV
- Citation
- Journal of Controlled Release, v. 330.0, Page. 1300-1312
- Abstract
- Excessive tumor necrosis factor-α (TNF-α) is associated with the pathogenesis of rheumatoid arthritis (RA). Approximately 90% of patients with RA, who have inadequate response to methotrexate, follow anti-TNF-α therapy as the first-line immuno-treatment. However, ineffective long-term anti-TNF-α antibody cycling for 40% of non-responders to anti-TNF-α antibodies is costly and associated with various side effects, which needs alternative mechanism of action therapies. In the present study, a novel strategy to down-regulate TNF-α level was developed by using an alternative method of suppressing TNF-α converting enzyme (TACE), a transmembrane enzyme involved in cleaving and releasing bioactive soluble TNF-α. TACE suppression can be an effective remedy to block the production of soluble TNF-α, leading to an increased sensitivity to anti-TNF-α non-responders. A disease site-targeted RNA interference system was developed by forming non-viral complex between shRNA against TACE (shTACE) and bone resorption site-specific peptide carrier composed of aspartate repeating and arginine repeating sequences. The shTACE/peptide carrier complex alleviated arthritic symptoms in collagen induced arthritis (CIA) models by demonstrating enhanced anti-inflammatory and anti-osteoclastogenic effects. Similar results were obtained with human primary synovial cells and osteoclast precursor isolated from tissues and synovial fluids of RA patients. Taken together, the shTACE/targeting peptide complex provides a strong potential as an alternative anti-TNF-α therapeutic for RA treatment. © 2020 Elsevier B.V.
- URI
- https://www.sciencedirect.com/science/article/pii/S016836592030691X?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/177542
- ISSN
- 0168-3659;1873-4995
- DOI
- 10.1016/j.jconrel.2020.11.041
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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