Lipopeptide delivery of siRNA to the central nervous system.
Lipopeptide delivery of siRNA to the central nervous system.
复制标题
脂肽将 siRNA 递送至中枢神经系统。
DOI：
10.1007/978-1-62703-140-0_17
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Zabel,MarkD
中科院分区：
文献类型：
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作者：
Zabel,MarkD
RNA干扰是一种相对较新的工具，用于沉默不同生物系统中的特定基因。由于缺乏一种将siRNA通过血脑屏障（BBB）传递到中枢神经系统（CNS）的有效途径，这项有前途的新技术在研究和治疗神经系统疾病方面的发展受到了阻碍。在这里，我们描述了一种通过与乙酰胆碱受体（AchRs）结合作为神经元地址的肽络合将siRNA递送到中枢神经系统的方法。在复合物中加入阳离子脂质体可以保护复合物免受途中血清核酸酶和蛋白酶的侵害。当静脉注射时，这些脂质体- siRNA -肽复合物抵抗血清降解，有效地穿过血脑屏障，并将siRNA传递到表达achr的细胞中，以抑制CNS中的蛋白质表达。
RNA interference is a relatively new tool used to silence specific genes in diverse biological systems. The development of this promising new technique for research and therapeutic use in studying and treating neurological diseases has been hampered by the lack of an efficient way to deliver siRNA transvascularly across the blood–brain barrier (BBB) to the central nervous system (CNS). Here we describe a method for delivering siRNA to the CNS by complexing it to a peptide that acts as a neuronal address by binding to acetylcholine receptors (AchRs). Adding cationic liposomes to the complex protects it from serum nucleases and proteases en route. When injected intravenously, these liposome–siRNA–peptide complexes resist serum degradation, effectively cross the BBB, and deliver siRNA to AchR-expressing cells to suppress protein expression in the CNS.