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We propose a novel therapeutic strategy using synthetic biology to reprogram macrophage responses. By engineering an inducible TET\u2010ON gene circuit to express immunomodulatory PeptideA (PepA), we enhance IL\u201012 production and parasite clearance. Peptides were identified via AI and validated through molecular dynamics simulations. This approach shifts macrophages toward a pro\u2010inflammatory M1 phenotype, improving infection outcomes. Delivery via Tac\u20106 nanogel and adoptive transfer enables\n                    <jats:italic>in vivo<\/jats:italic>\n                    expression. Our method offers targeted, controllable treatment for CL, potentially overcoming current limitations. This platform also provides a versatile pipeline for studying macrophage\u2010associated infections and inflammatory diseases, paving the way for precision immunotherapy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>We present a synthetic biology\u2010based approach to treat cutaneous leishmaniasis by reprogramming macrophages with an inducible gene circuit expressing AI\u2010designed peptides that boost IL\u201012 production and parasite clearance. Delivered via Tac\u20106 nanogel, this strategy offers targeted, resistance\u2010mitigating therapy and a versatile platform for macrophage\u2010driven diseases.<\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70254","type":"journal-article","created":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T12:30:21Z","timestamp":1766233821000},"page":"644-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthetic bioengineered macrophages for immune cell functions in infectious disease cellular therapy"],"prefix":"10.1002","volume":"600","author":[{"given":"Shweta","family":"Khandibharad","sequence":"first","affiliation":[{"name":"Systems Medicine Laboratory, BRIC\u2010National Centre for Cell Science  Pune 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