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• W2913894947 abstract "Abstract Biologic drug therapies are effective treatments for autoimmune diseases such as rheumatoid arthritis (RA) but may cause significant adverse effects, as they are administered continuously at high doses that can suppress the immune system. Using CRISPR-Cas9 genome editing, we engineered stem cells containing a synthetic gene circuit expressing biologic drugs to antagonize interleukin-1 (IL-1) or tumor necrosis factor (TNF) in an autoregulated, feedback-controlled manner in response to activation of the endogenous chemokine (C-C) motif ligand 2 (Ccl2) promoter. To test this approach in vivo, cells were tissue-engineered into a stable cartilaginous construct and implanted subcutaneously in mice with inflammatory arthritis. Bioengineered anti-cytokine implants mitigated arthritis severity as measured by joint pain, structural damage, and systemic and local inflammation. The coupling of synthetic biology with tissue engineering promises a range of potential applications for treating chronic diseases using custom-designed cells that express therapeutic transgenes in response to dynamically changing biological signals." @default.
• W2913894947 created "2019-02-21" @default.
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• W2913894947 date "2019-01-30" @default.
• W2913894947 modified "2023-09-25" @default.
• W2913894947 title "A Genome-engineered Bioartificial Implant for Autoregulated Anti-Cytokine Drug Delivery" @default.
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• W2913894947 doi "https://doi.org/10.1101/535609" @default.
• W2913894947 hasPublicationYear "2019" @default.
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