Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles.

Autor: Zickler AM; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden., Liang X; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Cancer Research Laboratory, Shandong University-Karolinska Institutet collaborative Laboratory, School of Basic Medical Science, Shandong University, No. 44, Wenhua Xi Road, Ji'nan, Shandong, 250012, P. R. China., Gupta D; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Institute of Developmental and Regenerative Medicine, Department of Paediatrics., University of Oxford, Old Road Campus, Roosevelt Dr, Headington, Oxford, OX3 7TY, UK., Mamand DR; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, 14186, Sweden., De Luca M; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK.; Human Technopole, Viale Rita Levi Montalcini, 1, Milan, 20157, Italy., Corso G; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Evercyte GmbH, Leberstrasse 20, Vienna, 1110, Austria., Errichelli L; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK., Hean J; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK., Sen T; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK.; Lonza Biologics, Chesterford Research Park, Cambridge, CB10 1XL, UK., Elsharkasy OM; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden., Kamei N; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Laboratory of Drug Delivery Systems, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe, Hyogo, 650-8586, Japan., Niu Z; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Five Jing Road, Ji'nan, Shandong, 250012, P. R. China., Zhou G; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Department of Gynecology, The Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Shanghai, 200011, P. R. China., Zhou H; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden., Roudi S; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden., Wiklander OPB; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, 14186, Sweden., Görgens A; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany., Nordin JZ; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Clinical Immunology and Transfusion Medicine (KITM), Karolinska University Hospital, Stockholm, 14186, Sweden., Castilla-Llorente V; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK.; Uncommon Bio, Cambridge Technopark, Newmarket Rd, Cambridge, CB5 8PB, UK., El Andaloussi S; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Sep 09, pp. e2407619. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1002/advs.202407619
Abstrakt: Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation and reduce immunogenicity. Here, a bioengineering platform for efficient mRNA loading and functional delivery using bionormal nanoparticles, extracellular vesicles (EVs), is established by expressing a highly specific RNA-binding domain fused to CD63 in EV producer cells stably expressing the target mRNA. The additional combination with a fusogenic endosomal escape moiety, Vesicular Stomatitis Virus Glycoprotein, enables functional mRNA delivery in vivo at doses substantially lower than currently used clinically with synthetic lipid-based nanoparticles. Importantly, the application of EVs loaded with effective cancer immunotherapy proves highly effective in an aggressive melanoma mouse model. This technology addresses substantial drawbacks currently associated with EV-based nucleic acid delivery systems and is a leap forward to clinical EV applications.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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