尽管非病毒核酸递送系统通常被认为比病毒载体效率低,近年来,与病毒对应物相比,它们具有优越的安全性,因此引起了人们的极大兴趣.这些合成载体是阳离子聚合物,支化树枝状聚合物,阳离子脂质体和细胞穿透肽(CPPs)。后者代表基本上特征在于高含量的碱性氨基酸和10-30个残基长度的相当不相关的序列的分类。CPPs能够介导亲水性大分子如肽和核酸的细胞摄取(例如siRNA,适体和反义寡核苷酸),当单独应用时,它们以非常低的速率被细胞内化。到目前为止,据报道,许多序列显示出细胞穿透特性,其中许多序列已被用于成功地将各种不同的货物运输到哺乳动物细胞中。近年来,很明显,内吞作用是内化的主要途径,尽管人们对CPPs细胞易位的潜在机制知之甚少,但仍有争议的讨论.在这次审查中,我们将总结核酸货物基于肽的细胞递送的最新进展。我们将讨论不同的进入机制,货物的细胞内命运,吸收与货物生物活性的相关性研究以及技术问题和陷阱。
Despite the fact that non-viral nucleic acid delivery systems are generally considered to be less efficient than viral vectors, they have gained much interest in recent years due to their superior safety profile compared to their viral counterpart. Among these synthetic vectors are cationic polymers, branched dendrimers, cationic liposomes and cell-penetrating peptides (CPPs). The latter represent an assortment of fairly unrelated sequences essentially characterised by a high content of basic amino acids and a length of 10-30 residues. CPPs are capable of mediating the cellular uptake of hydrophilic macromolecules like peptides and nucleic acids (e.g. siRNAs, aptamers and antisense-oligonucleotides), which are internalised by cells at a very low rate when applied alone. Up to now, numerous sequences have been reported to show cell-penetrating properties and many of them have been used to successfully transport a variety of different cargos into mammalian cells. In recent years, it has become apparent that endocytosis is a major route of internalisation even though the mechanisms underlying the cellular translocation of CPPs are poorly understood and still subject to controversial discussions. In this review, we will summarise the latest developments in peptide-based cellular delivery of nucleic acid cargos. We will discuss different mechanisms of entry, the intracellular fate of the cargo, correlation studies of uptake versus biological activity of the cargo as well as technical problems and pitfalls.