Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules
Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules
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DOI：
10.1042/bj20050401
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发表时间：
2005-09-01
影响因子：
4.1
通讯作者：
Cailler, F
中科院分区：
文献类型：
--
作者：
De Coupade, C;Fittipaldi, A;Cailler, F
短肽序列能够跨细胞膜运输分子，已被开发为细胞内递送治疗分子的工具。这项工作描述了一个新的细胞穿透肽家族，称为矢量细胞(R)肽[也称为DPVs（硅藻肽载体）]。这些多肽来源于人肝素结合蛋白和/或抗dna抗体，一旦结合到治疗分子上，就可以将治疗分子运送到哺乳动物细胞的细胞质或细胞核中。载体细胞(R)肽可以驱动不同分子质量的分子在细胞内传递，包括全长活性免疫球蛋白，其效率通常高于已被充分表征的细胞穿透肽Tat。载体细胞(R)肽的内化已被证明发生在贴壁和悬浮细胞系以及原代细胞中，通过能量依赖的内吞过程，包括细胞膜脂筏。这种内吞作用发生在细胞穿透肽与细胞外硫酸肝素蛋白聚糖结合之后，除了一种特殊的肽（DPV1047），它部分来源于抗dna抗体，并以一种独立于腔泡的方式内化。这些新的治疗工具目前正在开发，用于细胞内递送一些活性分子，并研究它们在体内转导的潜力。
Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell (R) peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell (R) peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell (R) peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.