Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia.
Laboratory of Intracellular Signaling, Moscow Institute of Physics and Technology, 141701 Moscow, Russia.
Cells. 2021 Nov 5;10(11):3043. doi: 10.3390/cells10113043.
The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape lysosomal destruction. Most artificial nanocarriers suffer from intrinsic limitations that prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and is usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and EVs. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with a higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into EVs.
精准医学的进展严重依赖于用于在人体内靶向递效应分子的载体的稳健性和特异性。已经在体内探索了许多纳米载体，以确保通过组织特异性靶向来精确递分子货物，包括胰腺、甲状腺和肾上腺的内分泌部分。然而，即使到达靶器官，载物载体也需要进入细胞，然后逃避溶酶体破坏。大多数人工纳米载体受到内在限制，阻止它们完成货物的特异性递。在这方面，由于其多功能性和低毒性，细胞外囊泡（EVs）似乎是递payload 的天然工具。然而，EV 介导的递是非选择性的，通常范围有限。通过将病毒膜融合蛋白插入外泌体中，可以提高膜识别的效率，并且还可以简化膜融合过程。本文描述了病毒辅助靶细胞与 EVs 之间相互作用的分子细节。我们还讨论了在开发具有更高递效率的基于细胞外囊泡的纳米载体时使用病毒融合蛋白的问题。最后，本文特别强调了 Gag 和 RNA 结合蛋白在 RNA 分选到 EVs 中的作用。
