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Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery

Delivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of the designed drugs. In this regard, natural membrane-based systems are of particular interest. Extracellular vesicles (EVs...

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Autores principales: Ovchinnikova, Leyla A., Terekhov, Stanislav S., Ziganshin, Rustam H., Bagrov, Dmitriy V., Filimonova, Ioanna N., Zalevsky, Arthur O., Lomakin, Yakov A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224366/
https://www.ncbi.nlm.nih.gov/pubmed/34064144
http://dx.doi.org/10.3390/pharmaceutics13060768
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author Ovchinnikova, Leyla A.
Terekhov, Stanislav S.
Ziganshin, Rustam H.
Bagrov, Dmitriy V.
Filimonova, Ioanna N.
Zalevsky, Arthur O.
Lomakin, Yakov A.
author_facet Ovchinnikova, Leyla A.
Terekhov, Stanislav S.
Ziganshin, Rustam H.
Bagrov, Dmitriy V.
Filimonova, Ioanna N.
Zalevsky, Arthur O.
Lomakin, Yakov A.
author_sort Ovchinnikova, Leyla A.
collection PubMed
description Delivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of the designed drugs. In this regard, natural membrane-based systems are of particular interest. Extracellular vesicles (EVs), being the bilayer lipid particles secreted by almost all types of cells, have several principal advantages: biocompatibility, carrier stability, and blood–brain barrier penetrability, which make them a perspective tool for protein therapeutic delivery. Here, we evaluate the engineered genetically encoded EVs produced by a human cell line, which allow efficient cargo loading. In the devised system, the protein of interest is captured by self-assembling structures, i.e., “enveloped protein nanocages” (EPN). In their turn, EPNs are encapsulated in fusogenic EVs by the overexpression of vesicular stomatitis virus G protein (VSV-G). The proteomic profiles of different engineered EVs were determined for a comprehensive evaluation of their therapeutic potential. EVs loading mediated by bio-safe Fos–Jun heterodimerization demonstrates an increased efficacy of active cargo loading and delivery into target cells. Our results emphasize the outstanding technological and biomedical potential of the engineered EV systems, including their application in adoptive cell transfer and targeted cell reprogramming.
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spelling pubmed-82243662021-06-25 Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery Ovchinnikova, Leyla A. Terekhov, Stanislav S. Ziganshin, Rustam H. Bagrov, Dmitriy V. Filimonova, Ioanna N. Zalevsky, Arthur O. Lomakin, Yakov A. Pharmaceutics Article Delivering protein therapeutics specifically into target cells and tissues is a promising avenue in medicine. Advancing this process will significantly enhance the efficiency of the designed drugs. In this regard, natural membrane-based systems are of particular interest. Extracellular vesicles (EVs), being the bilayer lipid particles secreted by almost all types of cells, have several principal advantages: biocompatibility, carrier stability, and blood–brain barrier penetrability, which make them a perspective tool for protein therapeutic delivery. Here, we evaluate the engineered genetically encoded EVs produced by a human cell line, which allow efficient cargo loading. In the devised system, the protein of interest is captured by self-assembling structures, i.e., “enveloped protein nanocages” (EPN). In their turn, EPNs are encapsulated in fusogenic EVs by the overexpression of vesicular stomatitis virus G protein (VSV-G). The proteomic profiles of different engineered EVs were determined for a comprehensive evaluation of their therapeutic potential. EVs loading mediated by bio-safe Fos–Jun heterodimerization demonstrates an increased efficacy of active cargo loading and delivery into target cells. Our results emphasize the outstanding technological and biomedical potential of the engineered EV systems, including their application in adoptive cell transfer and targeted cell reprogramming. MDPI 2021-05-21 /pmc/articles/PMC8224366/ /pubmed/34064144 http://dx.doi.org/10.3390/pharmaceutics13060768 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ovchinnikova, Leyla A.
Terekhov, Stanislav S.
Ziganshin, Rustam H.
Bagrov, Dmitriy V.
Filimonova, Ioanna N.
Zalevsky, Arthur O.
Lomakin, Yakov A.
Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title_full Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title_fullStr Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title_full_unstemmed Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title_short Reprogramming Extracellular Vesicles for Protein Therapeutics Delivery
title_sort reprogramming extracellular vesicles for protein therapeutics delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224366/
https://www.ncbi.nlm.nih.gov/pubmed/34064144
http://dx.doi.org/10.3390/pharmaceutics13060768
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