류마티즘 동물모델에서 대식세포에 특이적으로 TNF-α를 표적으로 하는 siRNA의 관절 주사 효능 연구

Abstract

Tumor necrosis factor-alpha (TNF-α) secreted from macrophage plays a central role in development of rheumatoid arthritis (RA). Although many therapeutic drugs are effective in controlling TNF-α, their side effects are occurred severe in patient systemically or orally -administrated inhibitor. To overcome current systemic delivery of anti TNF-α inhibitors, we evaluate intra-articular administration of siRNA targeting TNF-α (siTNF-α) complexed with RVG-9R, RVG-9R has been known to binds to acetylcholine receptor (AchR) which is expressed on macrophage. RVG-9R complexed with siTNF-α delivery functional siRNA to primary macrophage. Further, intra-articular administration of RVG-9R complexed with siTNF-α decrease clinical score of paw swelling significantly as well as joint destruction by reducing TNF-α level in a collagen antibody-induced arthritis (CAIA) mouse model of RA. These results indicate that macrophage specific suppression of TNF-α through intra-articular administration of RVG-9R complexed with siTNF-α can be used as a novel therapeutic intervention in rheumatoid arthritis minimizing unwanted side effects.