设计的Ankyrin重复蛋白质介导基核酸基础的预定目标:一项原则证明研究
Maryam Oroujeni1, Kristina Westerlund2, Eleftherios Papalanis1
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
概括
工程化支架蛋白称为设计的安基林重复蛋白 (DARPins) 现在可以用于预定向方法. 这种方法改善了瘤向,并减少了脏等器官的非向积累.
科学领域:
- 生物技术是生物技术.
- 分子成像学分子成像学
- 放射性药物疗法是一种放射性药物疗法.
背景情况:
- 设计的安基林重复蛋白 (DARP) 是小的,高亲和度的工程支架蛋白 (ESP),具有诊断和治疗的潜力.
- 目前的DARPin放射性免疫诊断因脏积累高而面临限制,阻碍了治疗应用.
- 基于核酸 (PNA) 的预定向已经在Affibody分子中取得了成功,这表明它适用于其他ESP.
研究的目的:
- 调查适用于DARPins的基于PNA的预定向策略的可行性.
- 开发和评估使用 HER2 向 DARPin G3.3 的预向系统.
- 为了比较基于DARPin的预先定位与直接定位和基于Affibody的预先定位的有效性.
主要方法:
- 通过酶A介导的结合,PNA与DARPin G3的局部特异性结合,产生了主干剂G3-HP1.
- 将G3-HP1标记为125I和一个补充PNA探头 (HP2) 标记为177Lu (含DOTA化剂).
- 试验室细胞结合测定,体内生物分布,以及在HER2阳性和阴性异种移植模型中的向特异性研究.
主要成果:
- 125 I-G3-HP1表现出特定的结合HER2表达细胞与皮科莫拉亲和力.
- 177Lu-HP2证明了HER2特异性,PNA依赖的结合到预处理的细胞,具有亚纳米系亲和力.
- 与直接向相比,预向增加了瘤吸收的8倍,并显著减少了脏,肝脏和脏的非向积累.
- 基于DARPin和Affibody的预定向显示了可比的生物分布和瘤吸收.
结论:
- 通过Sortase A介导的合成功地建立了一个基于PNA的预定向系统,用于DARPin G3.
- 这种方法将预定向的实用性扩展到另一个类型的工程支架蛋白.
- 基于DARPin的预定向提供了一种有希望的策略,用于在放射性免疫诊断和治疗中改善瘤向.
关键词:
177Lu 177Lu 177Lu 177Lu 177Lu 177Lu 177Lu 177Lu 177Lu 177Lu 177在DARPin G3中使用.在HER2中,HER2是HER2.在PNA中,PNA是PNA.这是一架SKOV-3战斗机.预定目标预定目标.更多相关视频
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