Erythropoietin gene delivery using an arginine-grafted bioreducible polymer system
Erythropoietin gene delivery using an arginine-grafted bioreducible polymer system
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DOI：
10.1016/j.jconrel.2011.10.014
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发表时间：
2012-02-10
影响因子：
10.8
通讯作者：
Bull, David A.
中科院分区：
文献类型：
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作者：
Nam, Hye Yeong;Lee, Youngsook;Bull, David A.
促红细胞生成素（EPO）在新红细胞（rbc）的形成中起着关键的调节作用。促红细胞生成素还可作为治疗神经、心脏和内皮细胞缺血性损伤的药物。阻碍促生成素治疗应用的一个限制是它的半衰期短。本研究的目的是开发一种基因传递系统，用于延长和控制EPO的释放。利用精氨酸接枝生物可还原聚合物（ABP）及其聚乙二醇化版本ABP- peg10，研究了该促红细胞生成素基因传递系统的体外表达效率和治疗效果。聚乙二醇（PEG）修饰ABP被用来抑制由阳离子多聚物与血清中典型存在的带负电荷的蛋白质之间的相互作用引起的颗粒聚集。ABP和ABP- peg10载体在多种细胞类型中均表现出高效转染和长期生成EPO的能力。表达的EPO蛋白在体外刺激造血祖细胞形成大量细胞集落。这些数据证实，这种使用生物可还原聚合物载体（ABP或ABP- peg 10）的EPO基因递送系统值得进一步测试，作为多种临床重要疾病状态的潜在治疗方式。(C) 2011 Elsevier B.V.版权所有
Erythropoietin (EPO) plays a key regulatory role in the formation of new red blood cells (RBCs). Erythropoietin may also have a role as a therapeutic agent to counteract ischemic injury in neural, cardiac and endothelial cells. One of the limitations preventing the therapeutic application of EPO is its short half-life. The goal of this study was to develop a gene delivery system for the prolonged and controlled release of EPO. The arginine grafted bioreducible polymer (ABP) and its PEGylated version, ABP-PEG10, were utilized to study the expression efficiency and therapeutic effectiveness of this erythropoietin gene delivery system in vitro. Poly (ethylene glycol) (PEG) modification of the ABP was employed to inhibit the particle aggregation resulting from the interactions between cationic polyplexes and the negatively charged proteins typically present in serum. Both the ABP and the ABP-PEG10 carriers demonstrated efficient transfection and long-term production of EPO in a variety of cell types. The expressed EPO protein stimulated hematopoietic progenitor cells to form significant numbers of cell colonies in vitro. These data confirm that this EPO gene delivery system using a bioreducible polymeric carrier, either ABP or ABP-PEG 10, merits further testing as a potential therapeutic modality for a variety of clinically important disease states. (C) 2011 Elsevier B.V. All rights reserved.