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Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C trachomatis\u2013infected cells, Z461X-CPP induced cell apoptosis in vitro. In an animal model, Z461X significantly shortened the duration of C trachomatis infection and prevented pathological damage in the mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C trachomatis infection.<\/jats:p>","DOI":"10.1093\/infdis\/jiae257","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T12:32:40Z","timestamp":1715257960000},"page":"1476-1487","source":"Crossref","is-referenced-by-count":4,"title":["Efficacy of a Novel Affitoxin Targeting Major Outer Membrane Protein Against <i>Chlamydia trachomatis<\/i> In Vitro and In Vivo"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-0857","authenticated-orcid":false,"given":"Mingyang","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University , Zhejiang 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