Cationic Nanoliposomes Meet mRNA

Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications

Tatjana Michel, Daniel Luft, Meike Kristin Abraham, Sabrina Reinhardt, Martha L. Salinas Medina, Julia Kurz, Martin Schaller, Meltem Avci-Adali, Christian Schlensak, Karlheinz Peter, Hans Peter Wendel, Xiaowei Wang, Stefanie Krajewski

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Synthetically modified mRNA is a unique bioactive agent, ideal for use in therapeutic applications, such as cancer vaccination or treatment of single-gene disorders. In order to facilitate mRNA transfections for future therapeutic applications, there is a need for the delivery system to achieve optimal transfection efficacy, perform with durable stability, and provide drug safety. The objective of our study was to comprehensively analyze the use of 3β-[N-(N',N'-dimethylaminoethane) carbamoyl](DC-Cholesterol)/dioleoylphosphatidylethanolamine (DOPE) liposomes as a potential transfection agent for modified mRNAs. Our cationic liposomes facilitated a high degree of mRNA encapsulation and successful cell transfection efficiencies. More importantly, no negative effects on cell viability or immune reactions were detected posttransfection. Notably, the liposomes had a long-acting transfection effect on cells, resulting in a prolonged protein production of alpha-1-antitrypsin (AAT). In addition, the stability of these mRNA-loaded liposomes allowed storage for 80 days, without the loss of transfection efficacy. Finally, comprehensive analysis showed that these liposomes are fully hemocompatible with fresh human whole blood. In summary, we present an extensive analysis on the use of DC-cholesterol/DOPE liposomes as mRNA delivery vehicles. This approach provides the basis of a safe and efficient therapeutic strategy in the development of successful mRNA-based drugs.

Original languageEnglish
Pages (from-to)459-468
Number of pages10
JournalMolecular Therapy - Nucleic Acids
Volume8
DOIs
Publication statusPublished - 15 Sep 2017

Cite this

Michel, Tatjana ; Luft, Daniel ; Abraham, Meike Kristin ; Reinhardt, Sabrina ; Salinas Medina, Martha L. ; Kurz, Julia ; Schaller, Martin ; Avci-Adali, Meltem ; Schlensak, Christian ; Peter, Karlheinz ; Wendel, Hans Peter ; Wang, Xiaowei ; Krajewski, Stefanie. / Cationic Nanoliposomes Meet mRNA : Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications. In: Molecular Therapy - Nucleic Acids. 2017 ; Vol. 8. pp. 459-468.
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abstract = "Synthetically modified mRNA is a unique bioactive agent, ideal for use in therapeutic applications, such as cancer vaccination or treatment of single-gene disorders. In order to facilitate mRNA transfections for future therapeutic applications, there is a need for the delivery system to achieve optimal transfection efficacy, perform with durable stability, and provide drug safety. The objective of our study was to comprehensively analyze the use of 3β-[N-(N',N'-dimethylaminoethane) carbamoyl](DC-Cholesterol)/dioleoylphosphatidylethanolamine (DOPE) liposomes as a potential transfection agent for modified mRNAs. Our cationic liposomes facilitated a high degree of mRNA encapsulation and successful cell transfection efficiencies. More importantly, no negative effects on cell viability or immune reactions were detected posttransfection. Notably, the liposomes had a long-acting transfection effect on cells, resulting in a prolonged protein production of alpha-1-antitrypsin (AAT). In addition, the stability of these mRNA-loaded liposomes allowed storage for 80 days, without the loss of transfection efficacy. Finally, comprehensive analysis showed that these liposomes are fully hemocompatible with fresh human whole blood. In summary, we present an extensive analysis on the use of DC-cholesterol/DOPE liposomes as mRNA delivery vehicles. This approach provides the basis of a safe and efficient therapeutic strategy in the development of successful mRNA-based drugs.",
author = "Tatjana Michel and Daniel Luft and Abraham, {Meike Kristin} and Sabrina Reinhardt and {Salinas Medina}, {Martha L.} and Julia Kurz and Martin Schaller and Meltem Avci-Adali and Christian Schlensak and Karlheinz Peter and Wendel, {Hans Peter} and Xiaowei Wang and Stefanie Krajewski",
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Michel, T, Luft, D, Abraham, MK, Reinhardt, S, Salinas Medina, ML, Kurz, J, Schaller, M, Avci-Adali, M, Schlensak, C, Peter, K, Wendel, HP, Wang, X & Krajewski, S 2017, 'Cationic Nanoliposomes Meet mRNA: Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications', Molecular Therapy - Nucleic Acids, vol. 8, pp. 459-468. https://doi.org/10.1016/j.omtn.2017.07.013

Cationic Nanoliposomes Meet mRNA : Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications. / Michel, Tatjana; Luft, Daniel; Abraham, Meike Kristin; Reinhardt, Sabrina; Salinas Medina, Martha L.; Kurz, Julia; Schaller, Martin; Avci-Adali, Meltem; Schlensak, Christian; Peter, Karlheinz; Wendel, Hans Peter; Wang, Xiaowei; Krajewski, Stefanie.

In: Molecular Therapy - Nucleic Acids, Vol. 8, 15.09.2017, p. 459-468.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - Efficient Delivery of Modified mRNA Using Hemocompatible and Stable Vectors for Therapeutic Applications

AU - Michel, Tatjana

AU - Luft, Daniel

AU - Abraham, Meike Kristin

AU - Reinhardt, Sabrina

AU - Salinas Medina, Martha L.

AU - Kurz, Julia

AU - Schaller, Martin

AU - Avci-Adali, Meltem

AU - Schlensak, Christian

AU - Peter, Karlheinz

AU - Wendel, Hans Peter

AU - Wang, Xiaowei

AU - Krajewski, Stefanie

PY - 2017/9/15

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