Neuberg Patrick, Kichler Antoine
Laboratoire "Vecteurs: Synthèse et Applications Thérapeutiques", UMR7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, Illkirch, France.
Adv Genet. 2014;88:263-88. doi: 10.1016/B978-0-12-800148-6.00009-2.
Polyethylenimines (PEIs) have proven to be highly efficient and versatile agents for nucleic acid delivery in vitro and in vivo. Despite the low biodegradability of these polymers, they have been used in several clinical trials and the results suggest that the nucleic acid/PEI complexes have a good safety profile. The high transfection efficiency of PEIs probably relies on the fact that these polymers possess a stock of amines that can undergo protonation during the acidification of endosomes. This buffering capacity likely enhances endosomal escape of the polyplexes through the "proton sponge" effect. PEIs have also attracted great interest because the presence of many amino groups allow for easy chemical modifications or conjugation of targeting moieties and hydrophilic polymers. In the present chapter, we summarize and discuss the mechanism of PEI-mediated transfection, as well as the recent developments in PEI-mediated DNA, antisense oligonucleotide, and siRNA delivery.
聚乙烯亚胺（PEIs）已被证明是用于体外和体内核酸递送的高效且通用的试剂。尽管这些聚合物的生物降解性较低，但它们已用于多项临床试验，结果表明核酸/PEI复合物具有良好的安全性。PEIs的高转染效率可能依赖于这样一个事实，即这些聚合物拥有大量的胺，在内体酸化过程中可发生质子化。这种缓冲能力可能通过“质子海绵”效应增强多聚体的内体逃逸。PEIs也引起了极大的兴趣，因为许多氨基的存在便于进行化学修饰或与靶向部分及亲水性聚合物结合。在本章中，我们总结并讨论了PEI介导的转染机制，以及PEI介导的DNA、反义寡核苷酸和siRNA递送的最新进展。
