Anti-PEG IgM Production via a PEGylated Nanocarrier System for Nucleic Acid Delivery
Anti-PEG IgM Production via a PEGylated Nanocarrier System for Nucleic Acid Delivery
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DOI：
10.1007/978-1-4939-9092-4_22
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发表时间：
2019-01-01
期刊：
影响因子：
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通讯作者：
Ishida, Tatsuhiro
中科院分区：
文献类型：
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作者：
Abu Lila, Amr S.;Ishida, Tatsuhiro
对于核酸[质粒DNA（pDNA）和小干扰RNA（siRNA）]的系统应用，需要克服核酸的不良药代动力学性质的安全且有效的载体。可以与核酸配制脂复合物的阳离子脂质体作为基因治疗中的有效递送系统具有重要前景。为了实现体内稳定性和长循环，大多数脂质复合物用PEG修饰（PEG化）。然而，我们报道了PEG化脂质体在同一动物中以一定间隔重复注射时失去了其长循环特性。这种意想不到的和不希望的现象被称为加速血液清除（ABC）现象。已证明，响应于第一剂量的PEG化脂质体产生的抗PEG IgM是ABC现象的主要原因。因此，在重复给药方案中，检测PEG化lipoplex处理动物中的抗PEG IgM对于预测ABC现象的发生可能至关重要。本章介绍了一种通过简单的ELISA程序评价血清抗PEG IgM的方法，并描述了与该方法相关的一些注意事项。
For the systemic application of nucleic acids [plasmid DNA (pDNA) and small interfering RNA (siRNA)], safe and efficient carriers that overcome the poor pharmacokinetic properties of nucleic acids are required. A cationic liposome that can formulate lipoplexes with nucleic acids has significant promise as an efficient delivery system in gene therapy. To achieve in vivo stability and long circulation, most lipoplexes are modified with PEG (PEGylation). However, we reported that PEGylated liposomes lose their longcirculating properties when they are injected repeatedly at certain intervals in the same animal. This unexpected and undesirable phenomenon is referred to as the accelerated blood clearance (ABC) phenomenon. Anti-PEG IgM produced in response to the first dose of PEGylated liposomes has proven to be a major cause of the ABC phenomenon. Therefore, in a repeated dosing schedule, the detection of anti-PEG IgM in an animal treated with PEGylated lipoplex could be essential to predict the occurrence of the ABC phenomenon. This chapter introduces a method for the evaluation of serum anti-PEG IgM by a simple ELISA procedure, and describes some precautions associated with this method.