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通过cell-SELEX获得的向APT8 (((16-34) 和其与miR-23-5p内部化到激活的肝星细胞中

Xue Yang^1,2,3, Lu Huang^1,2,3,4, Li-Qing Yang^1,3,5

¹Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Daxue Road 8#, Yichang, China.

Hepatology international

|December 16, 2024

概括

研究人员发现了一种新型的阿巴酶,APT8 ((16-34),它专门向激活的肝星状细胞. 当与miR-23b-5p结合时,这种阿巴酶有效地提供治疗有效载荷,以抑制肝纤维化进展.

科学领域:

生物化学生物化学
分子生物学分子生物学
肝病学肝病学是一种肝病学.

背景情况:

肝星细胞的激活是肝纤维化病原体的核心.
针对这些激活细胞对于开发有效的抗纤维性疗法至关重要.
目前的治疗策略缺乏针对激活的肝星细胞的特定输送工具.

研究的目的:

为了确定针对激活的肝星状细胞的特定向体.
开发一种针对性提供抗纤维菌剂的系统.
评估在肝纤维化中aptamer-药物合物的治疗潜力.

主要方法:

在HSC-T6细胞系上通过指数式丰富 (SELEX) 系统地演变连接体.
为了提高特异性和亲和力,Aptamer的缩减和优化.
优化aptamer (APT8(16-34) 与miR-23b-5p的结合,用于有针对性的输送.

主要成果:

鉴定了11种aptamer候选物 (APT1-11),其中APT8(16-34) 在体外和体内对激活的肝星细胞具有很高的特异性.
APT8 (((16-34) 在与miR-23b-5p.p.结合后被证明可以内化到激活的肝星细胞中.
交付的miR-23b-5p有效抑制了目标mRNA转化,降低了与纤维化相关的蛋白质的调节.

结论:

APT8 ((16-34) 是一种针对激活的肝星细胞的特定向和内化剂.
APT8 ((16-34) -miR-23b-5p结合物促进了miR-23b-5p在目标细胞中的功能传递.
这种方法对开发针对性治疗肝纤维化有希望.

关键词:

亚普特美尔 (Aptamer) 是一种药物.肝脏纤维化肝脏纤维化肝脏的星状细胞.在 miR-23b-5p 中.

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