Gorshkov Andrey, Purvinsh Lada, Brodskaia Alexandra, Vasin Andrey
Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, 197376 Saint Petersburg, Russia.
Laboratory of Pathomorphology, Almazov National Research Centre, 197341 Saint Petersburg, Russia.
Nanomaterials (Basel). 2022 Feb 2;12(3):524. doi: 10.3390/nano12030524.
Exosomes are natural nanocontainers actively secreted by the body's cells and transmitting molecular signals of various types to recipient cells. Cellular mechanisms of exosomes' biogenesis involve specific sorting of RNA for incorporation into them. As a result, the molecular composition of exosomes is closely related to the donor cell's functional state, and this makes exosomes an important diagnostic and prognostic marker in a number of diseases (primarily oncological). The ability of exosomes to transport biologically active molecules and to protect the cargo from degradation makes them nearly ideal candidates as delivery carriers of RNA in therapeutic or prophylactic regimes. Potential of exosomal surface functionalization enables improved targeting to specific organs, tissues and cells. However, the development of an effective technology for RNA's loading into exosomes cannot be considered resolved. This review is focused on experimental data on the use of exosomes as vehicles for the delivery of therapeutic and prophylactic RNAs. We briefly consider the biogenesis and functions of exosomes, focusing on those biological properties that make them formidable candidates in the race to develop effective delivery carriers. Furthermore, we describe various techniques of cargo loading into exosomes. Prospects of exosomes application as therapeutic delivery system for siRNAs, miRNAs, and long RNAs are considered.
外泌体是机体细胞主动分泌的天然纳米容器，可向受体细胞传递各种类型的分子信号。外泌体生物发生的细胞机制涉及RNA的特定分选以纳入其中。因此，外泌体的分子组成与供体细胞的功能状态密切相关，这使得外泌体成为许多疾病（主要是肿瘤疾病）重要的诊断和预后标志物。外泌体运输生物活性分子并保护所载物质不被降解的能力使其几乎成为治疗或预防方案中RNA递送载体的理想候选者。外泌体表面功能化的潜力能够实现对外泌体向特定器官、组织和细胞的更好靶向。然而，将RNA有效加载到外泌体中的技术发展仍未得到解决。本综述聚焦于有关将外泌体用作治疗性和预防性RNA递送载体的实验数据。我们简要考虑外泌体的生物发生和功能，重点关注那些使其在开发有效递送载体的竞争中成为有力候选者的生物学特性。此外，我们描述了将物质加载到外泌体中的各种技术。还探讨了外泌体作为siRNA、miRNA和长链RNA治疗性递送系统的应用前景。
