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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. In this study, a genetically engineered biomimetic membrane\u2010coated mRNA (MR@P\u2010mPTEN) carrier that effectively delivers mRNA\u2010PTEN (mPTEN) directly to the RA joint is presented. By overexpressing tumor necrosis factor (TNF\u2010\u03b1) receptors on macrophage biomimetic membranes via plasmid transfection, decoys that reduce inflammatory pathway activation are prepared for TNF\u2010\u03b1. The resulting construct, MR@P\u2010mPTEN, shows good stability and RA targeting based on in vivo fluorescence imaging. It is also found that MR@P\u2010mPTEN competitively binds TNF\u2010\u03b1 and activates the PTEN pathway in vitro and in vivo, thereby inhibiting synovitis and joint damage. Clinical micro\u2010computed tomography and histological analyses confirm the treatment effects. These results suggest that the genetically engineered biomimetic therapeutic platform MR@P\u2010mPTEN both inhibits pro\u2010inflammatory cytokines and upregulates PTEN protein expression to alleviate RA damage, providing a new a new combination strategy for RA treatment.<\/jats:p>","DOI":"10.1002\/smtd.202300678","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T12:10:45Z","timestamp":1690891845000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Genetically Engineered Biomimetic Nanoparticles for Targeted Delivery of mRNA to Treat Rheumatoid Arthritis"],"prefix":"10.1002","volume":"7","author":[{"given":"Jianhai","family":"Chen","sequence":"first","affiliation":[{"name":"Center for Translational Medicine Research and Development Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"},{"name":"Research Center for Biomedical Optics and Molecular Imaging CAS Key Laboratory of Health Informatics Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"},{"name":"Rehabilitation Department of The Second Affiliated Hospital School of Medicine The Chinese University of Hong Kong Shenzhen &amp; Longgang District People's Hospital of Shenzhen  Shenzhen 518172 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Tan","sequence":"additional","affiliation":[{"name":"Research Center for Biomedical Optics and Molecular Imaging CAS Key Laboratory of Health Informatics Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine Research and Development Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine Research and Development Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Ke","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine Research and Development Shenzhen Institute of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Department of The Second Affiliated Hospital School of Medicine The Chinese University of Hong Kong Shenzhen &amp; Longgang District People's Hospital of Shenzhen  Shenzhen 518172 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Department of The Second Affiliated Hospital School of Medicine The Chinese University of Hong Kong Shenzhen &amp; Longgang District People's Hospital of Shenzhen  Shenzhen 518172 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sien","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Stem Cells and Regenerative Medicine Laboratory Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Prince of Wales Hospital  Shatin 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Stem Cells and Regenerative Medicine Laboratory Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong Prince of Wales Hospital  Shatin 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Rehabilitation Department of The Second Affiliated Hospital School of Medicine The Chinese University of Hong Kong Shenzhen &amp; 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