...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleic Acid Therapeutics >A Single Dose of EGLN1 siRNA Yields Increased Erythropoiesis in Nonhuman Primates
【24h】

A Single Dose of EGLN1 siRNA Yields Increased Erythropoiesis in Nonhuman Primates

机译：单一剂量的EGLN1 siRNA会增加非人类灵长类动物的促红细胞生成作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Decreased production of erythropoietin (EPO) causes anemia in patients with chronic kidney disease, and recombinant human EPO is used to treat renal failure associated anemia. The liver, the main EPO-producing organ in utero, maintains the capacity to produce EPO in the adult but in insufficient quantities to restore hemoglobin levels to normal in patients with impaired renal function. Inhibition of prolyl-4-hydroxylase domain (PHD) proteins is known to cause an increase in EPO production through its effects on hypoxia inducible factor. Here, we utilized small interfering RNA (siRNA) targeting EGLN1, the gene encoding the PHD2 protein, to investigate the phenotypic consequences in nonhuman primates. A single, well-tolerated intravenous dose of an optimized EGLN1 siRNA encapsulated in a lipid nanoparticle formulation caused robust mRNA silencing in the liver, leading to increases in serum EPO and hemoglobin. The siRNA-induced erythropoiesis was dose-dependent and was sustained for at least 2 months. These data point to the potential for an RNA interference-based, liver-targeted therapeutic approach for the treatment of anemia.
机译：促红细胞生成素（EPO）产量减少会导致慢性肾脏病患者出现贫血，重组人EPO用于治疗肾衰竭相关的贫血。肝脏是子宫内产生EPO的主要器官，它可以维持成人产生EPO的能力，但数量不足以使肾功能受损的患者的血红蛋白水平恢复正常。已知脯氨酰-4-羟化酶结构域（PHD）蛋白的抑制通过其对缺氧诱导因子的作用而引起EPO产生增加。在这里，我们利用针对EGLN1（编码PHD2蛋白的基因）的小干扰RNA（siRNA）来研究非人类灵长类动物的表型后果。封装在脂质纳米颗粒制剂中的单一，耐受性良好的静脉内剂量的优化EGLN1 siRNA在肝脏中引起强大的mRNA沉默，从而导致血清EPO和血红蛋白增加。 siRNA诱导的红细胞生成是剂量依赖性的，并持续至少2个月。这些数据表明了基于RNA干扰，肝靶向治疗贫血的治疗方法的潜力。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号