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

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 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.

An exosome-related lncRNA signature correlates with prognosis, immune microenvironment, and therapeutic responses in hepatocellular carcinoma

“…This correlation might suggest a mechanism for lncRNAs to regulate exosome formation. RNA-binding proteins are involved in transferring RNA into exosomes [ 52 ]. We found that the modeling lncRNAs were extensively correlated with 1055 OS-related RBP genes.…”

The local variation of the Gaussian modulus enables different pathways for fluid lipid vesicle fusion

“…At that point, a refolding brings the two membranes in close contact and the fusion process can proceed towards the opening of a pore, passing through a hemifusion intermediate [49]. The insertion of a HA fusion peptide releases about 13 k B T , thus the action of three neighboring HA trimers is thought to generate enough energy to perturb the bilayer and overcome the dehydration barrier that keeps the two membranes apart [50], a task also accomplished by increasing the protrusion of lipid tails [51]. Thus, this energy released upon insertion can be used to move from the zeroth stage of fusion [38] to the following one.…”

Genetically Encoded Self-Assembling Protein Nanoparticles for the Targeted Delivery In Vitro and In Vivo

“…There are different approaches to the classification of VLPs, depending on the presence of lipid envelopes (enveloped and non-enveloped) and on the form (helical, icosahedral, spherical, and complex) and the number of capsid layers (1, 2, and more). Small size, wide possibilities of surface modification, high biocompatibility, various ways of VLP production, the possibility of incorporating various chemicals inside—all these factors open up wide possibilities for the application of the virus-like particles, including the creation of vaccines, delivery of drugs, genes, proteins, and other chemicals [ 171 , 172 , 173 , 174 ].…”