Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.
Appl Biochem Biotechnol. 2013 Jan;169(1):159-69. doi: 10.1007/s12010-012-9962-7. Epub 2012 Nov 17.
Delivery of therapeutic proteins into tissues and across the blood-brain barrier (BBB) is limited by the size and biochemical properties of the proteins. Efficient delivery across BBB is generally restricted to small, highly lipophilic molecules. However, in the last decades, several peptides that can pass cell membranes have been identified. It has been shown that these peptides are also capable of delivering large hydrophilic cargoes into cells and are therefore a powerful biological tool for transporting drugs across cell membranes and even into the brain. We designed and prepared a single-chain antibody fragment (scFvs), specific for the pathological form of the prion protein (PrP(Sc)), where a cell-penetrating peptide (CPP) was used as a linker between the two variable domains of the scFv. The intravenously administered recombinant scFv-CPP was successfully targeted to and delivered into mouse brain cells. Our single-chain antibody fragments are of special interest in view of possible therapeutic reagents design not only for prion diseases but also for other neurodegenerative diseases.
将治疗性蛋白质递送到组织中和穿过血脑屏障（BBB）受到蛋白质的大小和生化特性的限制。高效地穿过 BBB 通常仅限于小的、高度亲脂性的分子。然而，在过去几十年中，已经鉴定出几种可以穿过细胞膜的肽。已经表明，这些肽也能够将大的亲水性货物递送到细胞中，因此它们是一种强大的生物工具，可用于将药物穿过细胞膜甚至递送到大脑中。我们设计并制备了针对朊病毒蛋白（PrP(Sc)）的病理形式的单链抗体片段（scFv），其中细胞穿透肽（CPP）用作 scFv 的两个可变结构域之间的连接物。静脉内给予的重组 scFv-CPP 成功地靶向并递送到小鼠脑细胞中。鉴于可能的治疗试剂设计，我们的单链抗体片段不仅对朊病毒病，而且对其他神经退行性疾病都具有特殊的兴趣。
