推进凝血治疗的新型高 afinity 血栓吸收剂:平衡血栓抑制以预防凝血和有效的血液管理与抗剂
Mohamad Ammar Ayass1, Natalya Griko1, Victor Pashkov1
1Ayass Bioscience LLC, 8501 Wade Blvd, Building 9, Frisco, TX 75034, USA.
Cells
|September 28, 2023
概括
新的血蛋白DNA吸收体显示出抑制血液凝固的高度亲和力和特异性. 这些体是稳定,安全和可逆的,为抗凝治疗提供了有前途的潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 热血素是血液凝固中的关键酶.
- 血栓的失调有助于发生诸如中风和心肌梗塞等血栓性疾病.
- 热血素体为抗凝血提供了潜在的治疗策略.
研究的目的:
- 开发和表征用于治疗应用的新型ombin DNA 吸收体.
- 在体外 (in vitro) 评估这些阿普坦的疗效,特异性,稳定性和安全性.
- 评估一种抗毒剂的可行性,以控制阿普他默诱导的抗凝血.
主要方法:
- 发展出血栓DNA的吸收体.
- 在体外测试测量II因子活性,前列血时间 (PT) 和激活的部分血栓形成时间 (APTT).
- 使用平衡分离常数 (Kd) 确定亲和力.
- 在体外血和全血中进行稳定性评估.
- 对原体和免疫原体影响的安全评估.
- 开发一个反向补充序列作为解药.
主要成果:
- 发育的亚体AYA1809002和AYA1809004具有很高的亲和力 (Kd分别为10nM和13nM).
- 阿普塔默显著降低了血和全血中的II因子活性,并延长了血和全血中的PT和APTT时间.
- 在体外活动表明剂量依赖的疗效.
- 在生物矩阵中,aptamers在长达24小时的时间内保持稳定.
- 没有观察到变种或免疫效应,表明安全性.
- 反向补充序列有效地逆转了阿巴胺诱导的抗凝.
结论:
- 新型ombin DNA 体表现出ombin 活性的强大,特异性和稳定性抑制.
- 这些体对抗凝血疗法有显著的前景.
- 有可逆抗毒剂的可用性提高了安全性和治疗潜力.
- 进一步的开发可能会导致对血栓性疾病的新疗法.
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