Targeted therapy is an attractive approach for treating infectious diseases. 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-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

中文翻译：

---

新型 Affitoxin 靶向 MOMP 对沙眼衣原体的体外和体内功效

靶向治疗是治疗传染病的一种有吸引力的方法。 Affibody 分子具有与抗体相似的能力，可促进诊断和治疗应用中的分子识别。靶向主要外膜蛋白（MOMP）来治疗沙眼衣原体（最常见的性传播病原体之一）感染是一种有前途的治疗方法。此前，我们报道了噬菌体展示库中的 MOMP 特异性亲和体 (ZMOMP:461)。在这里，我们首先将其与修饰的假单胞菌外毒素 (PE38KDEL) 和细胞穿透肽 (CPP) 融合，开发出一种亲和毒素 Z461X-CPP。然后我们验证了毒素和 CPP 的添加不会影响 ZMOMP:461 与 MOMP 的亲和能力。 Z461X-CPP 被沙眼衣原体感染的细胞摄取后，可在体外诱导细胞凋亡。在动物模型中，Z461X显着缩短沙眼衣原体感染的持续时间并预防小鼠生殖系统的病理损伤。这些发现提供了令人信服的证据，表明 MOMP 特异性亲和毒素在沙眼衣原体感染的靶向治疗方面具有巨大潜力。