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Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles.
Zickler, Antje M; Liang, Xiuming; Gupta, Dhanu; Mamand, Doste R; De Luca, Mariacristina; Corso, Giulia; Errichelli, Lorenzo; Hean, Justin; Sen, Titash; Elsharkasy, Omnia M; Kamei, Noriyasu; Niu, Zheyu; Zhou, Guannan; Zhou, Houze; Roudi, Samantha; Wiklander, Oscar P B; Görgens, André; Nordin, Joel Z; Castilla-Llorente, Virginia; El Andaloussi, Samir.
Afiliación
  • Zickler AM; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Liang X; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Gupta D; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Mamand DR; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • De Luca M; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Corso G; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Errichelli L; 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.
  • Hean J; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Sen T; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Elsharkasy OM; Institute of Developmental and Regenerative Medicine, Department of Paediatrics., University of Oxford, Old Road Campus, Roosevelt Dr, Headington, Oxford, OX3 7TY, UK.
  • Kamei N; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Niu Z; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Zhou G; Karolinska ATMP Center, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Zhou H; Breast Center, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Roudi S; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK.
  • Wiklander OPB; Human Technopole, Viale Rita Levi Montalcini, 1, Milan, 20157, Italy.
  • Görgens A; Division of Biomolecular and Cellular Medicine, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Alfred-Nobels-Allé 8, Huddinge, Stockholm, 14152, Sweden.
  • Nordin JZ; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, 14186, Sweden.
  • Castilla-Llorente V; Evercyte GmbH, Leberstrasse 20, Vienna, 1110, Austria.
  • El Andaloussi S; Evox Therapeutics Ltd., Oxford Science Park, Medawar Centre, Robert Robinson Avenue, Oxford, OX4 4HG, UK.
Adv Sci (Weinh) ; : e2407619, 2024 Sep 09.
Article en En | MEDLINE | ID: mdl-39246205
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Alemania