Toloue Masoud M, Ford Lance P
Bioo Scientific Corporation, 78744, Austin, TX, USA.
Methods Mol Biol. 2011;764:123-39. doi: 10.1007/978-1-61779-188-8_8.
It is very clear that RNA interference (RNAi) is a potent and versatile tool for gene silencing. One of the hurdles to making siRNA/miRNA a human therapeutic includes effective in vivo delivery and being able to deliver drugs to target cells only. The commercial success of in vivo applications of RNAi hinges on the development of new delivery methods. Our strategy involves the use of antibody-based delivery agents to target and deliver siRNA into specific cell types. We have developed antibody-based agents for directed delivery into cultured cells and animal disease models. Using antibodies against various cell surface receptors, modified siRNAs are attached to antibody complexes using RNA carrier proteins. The complex can then be intravenously administered to in vivo models and taken up by specific cells via receptor-mediated endocytosis. The labile structure of the linking agents enables release of siRNA molecules post internalization. Using this targeting strategy, we have developed a method that allows any commercially available or recombinant antibody to be conjugated to siRNA for delivery purposes.
很明显，RNA干扰（RNAi）是一种强大且通用的基因沉默工具。使siRNA/miRNA成为人类治疗药物的障碍之一包括有效的体内递送以及仅能将药物递送至靶细胞。RNAi体内应用的商业成功取决于新递送方法的开发。我们的策略涉及使用基于抗体的递送剂将siRNA靶向并递送至特定细胞类型。我们已经开发出基于抗体的试剂用于定向递送至培养细胞和动物疾病模型。利用针对各种细胞表面受体的抗体，使用RNA载体蛋白将修饰的siRNA连接到抗体复合物上。然后可以将该复合物静脉内施用于体内模型，并通过受体介导的内吞作用被特定细胞摄取。连接剂的不稳定结构使得内化后siRNA分子能够释放。使用这种靶向策略，我们已经开发出一种方法，允许任何市售或重组抗体与siRNA缀合用于递送目的。
