دورية أكاديمية
TOP-EVs: Technology of Protein delivery through Extracellular Vesicles is a versatile platform for intracellular protein delivery.
| العنوان: | TOP-EVs: Technology of Protein delivery through Extracellular Vesicles is a versatile platform for intracellular protein delivery. |
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| المؤلفون: | Ilahibaks NF; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., Ardisasmita AI; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., Xie S; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., Gunnarsson A; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Mölndal 43183, Sweden., Brealey J; NanoFCM Co., Ltd, MediCity, D6 Thane Road, Nottingham NG906BH, United Kingdom., Vader P; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands; CDL Research, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., de Jong OG; Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Utrecht 3584 CG, the Netherlands., de Jager S; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., Dekker N; Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Mölndal 43183, Sweden., Peacock B; NanoFCM Co., Ltd, MediCity, D6 Thane Road, Nottingham NG906BH, United Kingdom., Schiffelers RM; CDL Research, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands., Sluijter JPG; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands; Circulatory Health Laboratory, Regenerative Medicine Center, University Medical Center Utrecht, University Utrecht, Utrecht 3584 CX, the Netherlands. Electronic address: j.sluijter@umcutrecht.nl., Lei Z; Laboratory of Experimental Cardiology, Department Heart & Lungs, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands; CDL Research, University Medical Center Utrecht, Utrecht 3584 CX, the Netherlands. Electronic address: zlei@umcutrecht.nl. |
| المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Mar; Vol. 355, pp. 579-592. Date of Electronic Publication: 2023 Feb 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| مواضيع طبية MeSH: | Extracellular Vesicles*/metabolism, Cell Communication ; Drug Delivery Systems/methods ; Endosomes ; Technology |
| مستخلص: | Extracellular vesicles (EVs) have emerged as biocompatible drug delivery vehicles due to their native ability to deliver bioactive cargo to recipient cells. However, the application of EVs as a therapeutic delivery vehicle is hampered by effective methods for endogenously loading target proteins inside EVs and unloading proteins after delivery to recipient cells. Most EV-based engineered loading methods have a limited delivery efficiency owing to their inefficient endosomal escape or cargo release from the intraluminal attachment from the EV membrane. Here, we describe the 'Technology Of Protein delivery through Extracellular Vesicles' (TOP-EVs) as a tool for efficient intracellular delivery of target proteins mediated via EVs. The vesicular stomatitis virus glycoprotein and the rapamycin-heterodimerization of the FKBP12/T82L mutant FRB proteins were both important for the effective protein delivery through TOP-EVs. We showed that TOP-EVs could efficiently deliver Cre recombinase and CRISPR/Cas9 ribonucleoprotein complex in vitro. Moreover, our results demonstrated that the capacity of TOP-EVs to deliver intracellular proteins in recipient cells was not an artifact of plasmid contamination or direct plasmid loading into EVs. Finally, we showed that TOP-EVs could successfully mediate intracellular protein delivery in the liver in vivo. Taken together, TOP-EVs are a versatile platform for efficient intracellular protein delivery in vitro and in vivo, which can be applied to advance the development of protein-based therapeutics. Competing Interests: Declaration of Competing Interest P.V. serves on the scientific advisory board of Evox Therapeutics. (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Active protein loading; Extracellular vesicles; Functional intracellular protein delivery; Genome editing; TOP-EV |
| تواريخ الأحداث: | Date Created: 20230206 Date Completed: 20230313 Latest Revision: 20230331 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.jconrel.2023.02.003 |
| PMID: | 36746337 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4995 |
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| DOI: | 10.1016/j.jconrel.2023.02.003 |