Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovial inflammation and joint destruction. Recently, a research group led by Prof. ZHANG Peng and Associate Prof. CHEN Jingqin at the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has reported new combination strategy for RA treatment. 

The study was published in Small Methods on Aug. 1.   

In addition to inhibiting persistent inflammation, phosphatase and tensin homolog deleted from chromosome 10 (PTEN) is known as an important therapeutic target for alleviating RA symptoms. Modulation of PTEN gene expression in synovial tissue using messenger RNA (mRNA) is a promising approach to combat RA. However, mRNA therapeutics are often hampered by unsatisfactory stability and inefficient localization in synovial tissue. Tumor necrosis factor (TNF-α) is considered to be a key inflammatory factor in targeted therapy of RA. 

In this study, a genetically engineered macrophage biomimetic membrane-coated mRNA (MR@P-mPTEN) carrier that effectively delivers mRNA-PTEN (mPTEN) directly to the RA joint is presented. By overexpressing TNF-α receptors on macrophage biomimetic membranes via plasmid transfection, decoys that reduce inflammatory pathway activation are prepared for TNF-α.   

The in vivo fluorescence imaging results indicate that MR@P-mPTEN shows good stability and RA targetine. It is also found that MR@P-mPTEN competitively binds TNF-α and activates the PTEN pathway in vitro and in vivo, thereby inhibiting synovitis and joint damage. Clinical micro-computed tomography and histological analyses confirm the treatment effects. 

"Our study offers a novel genetically engineered macrophage biomimetic therapeutic approach for the management of RA and a novel combined therapeutic paradigm for RA research in the future," said Prof. ZHANG. 

    The schedule introduction of this research. (Image by SIAT) 

Media Contact:
ZHANG Xiaomin
Email:xm.zhang@siat.ac.cn