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.
Highlights
Recent developments in precision medicine are largely due to the successful implementation of specific delivery of biologically active cargos to the target tissues
There are four key domains found in all Gag proteins: the matrix (MA) domain, which is primarily associated with membrane-binding capability; the capsid (CA) domain, which mediates numerous Gag–Gag interactions; the nucleocapsid (NC) domain, which is involved in packaging the genome RNA; and p6, which contributes to the release of the assembled particle from the host cell by interacting with the cellular endosomal sorting complexes required for transport (ESCRT)
An understanding of the mechanisms of membrane fusion and RNA sorting promises new approaches to control the loading of extracellular vesicles (EVs) with specific RNAs
Summary
Recent developments in precision medicine are largely due to the successful implementation of specific delivery of biologically active cargos to the target tissues. They enter a cell via an endocytosis-based pathway Natural carriers such as exosomes, on the contrary, have a complex surface composition with a specific set of membrane proteins that assist efficient targeting and entrance into the cells. Altering the lipid composition of membranes or modifications thereof with different energy-decreasing molecules enhances their nonspecific fusion with other membranes [21,22] It does not come as a surprise that liposome-based strategies have very limited efficacy for systemic delivery. Cell to cell communication is carried out through direct interaction, secretion of various soluble factors or different cell vesicles that can have an impact on other cells Such vesicles regulate fundamental biological properties in multiple ways, merging their membrane contents into the recipient cell plasma membrane and delivering effectors including transcription factors, oncogenes, small and large non-coding regulatory RNAs, mRNAs and infectious particles into recipient cells. This information may help to design novel approaches for the specific and efficient delivery of the molecular load, in particular miRNA, to manipulate the gene expression in the target cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
