Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes

Version 1 : Received: 6 October 2021 / Approved: 8 October 2021 / Online: 8 October 2021 (09:21:36 CEST)

How to cite: Zubarev, I.; Vladimirtsev, D.; Vorontsova, M.; Blatov, I.; Shevchenko, K.; Zvereva, S.; Lunev, E.A.; Faizuloev, E.; Barlev, N. Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes. Preprints 2021, 2021100130 (doi: 10.20944/preprints202110.0130.v1). Zubarev, I.; Vladimirtsev, D.; Vorontsova, M.; Blatov, I.; Shevchenko, K.; Zvereva, S.; Lunev, E.A.; Faizuloev, E.; Barlev, N. Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes. Preprints 2021, 2021100130 (doi: 10.20944/preprints202110.0130.v1).

Abstract

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 from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either 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 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 extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.

Keywords

fusion protein; extracellular vesicles; target delivery; RNA sorting

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