新开发的siRNA和DNA修复基因复发的药代动力学、生物分布和治疗应用

Madkour Lh
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引用次数: 0

摘要

细胞周期调节和DNA修复基因的上调似乎对甲状腺乳头状癌患者的无复发生存有负面影响。此外,复发与甲状腺去分化有关。大多数病例涉及过滤器官的局部应用或疾病,反映了siRNA的全身递送仍然存在挑战。小干扰RNA (Small Interfering RNA, siRNA)是一种很有前景的候选药物,有望在包括病毒感染和癌症在内的多种疾病中具有广泛的治疗潜力。随着近年来生物偶联化学和载体技术的进步,一些基于sirna的药物已经进入临床试验阶段。siRNA递送的困难在很大程度上是由于siRNA的循环稳定性差以及不利的药代动力学和生物分布特征。在本研究中,我们描述了siRNA纳米药物的药代动力学和生物分布,重点介绍了过去5年报道的siRNA纳米药物,以及它们在肝癌、肝脏感染和呼吸系统疾病等选定疾病模型中的药理作用。这里讨论的例子将提供对siRNA递送的现状和未满足需求的见解。
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Pharmacokinetics, Bio Distribution and Therapeutic Applications of Recently-Developed siRNA and DNA Repair Genes Recurrence
Up regulation of cell cycle-regulating and DNA repair genes appears to have a negative impact on recurrence-free survival in patients with papillary thyroid cancer. Furthermore, recurrence is associated with thyroid dedifferentiation. Most cases address local applications or diseases in the filtering organs, reflecting remaining challenges in systemic delivery of siRNA. Small Interfering RNA (siRNA) is a promising drug candidate, expected to have broad therapeutic potentials toward various diseases including viral infections and cancer. With recent advances in bio conjugate chemistry and carrier technology, several siRNA-based drugs have advanced to clinical trials. The difficulty in siRNA delivery is in large part due to poor circulation stability and unfavorable pharmacokinetics and bio distribution profiles of siRNA. In this research we describe the pharmacokinetics and bio distribution of siRNA Nano medicines, focusing on those reported in the past 5 years, and their pharmacological effects in selected disease models such as hepatocellular carcinoma, liver infections, and respiratory diseases. The examples discussed here will provide an insight into the current status of the art and unmet needs in siRNA delivery.
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