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Review
. 2020 Feb 20;10(2):364.
doi: 10.3390/nano10020364.

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Itziar Gómez-Aguado  1 , Julen Rodríguez-Castejón  1 , Mónica Vicente-Pascual  1 , Alicia Rodríguez-Gascón  1 , María Ángeles Solinís  1 , Ana Del Pozo-Rodríguez  1
Affiliations
Review

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Itziar Gómez-Aguado et al. Nanomaterials (Basel). .

Abstract

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

Keywords: Chimeric Antigen Receptor (CAR) T cells; cancer immunotherapy; dendritic cells; gene editing; gene therapy; immunotherapy; in vitro transcribed messenger RNA (IVT mRNA); infectious disease vaccines; nanomedicine; protein replacement.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Intracellular barriers for in vitro transcribed (IVT) mRNA delivery: (1) Interaction between the delivery system and cell membrane, (2) endocytosis, and (3) endosomal escape and release of the mRNA to start the translation process.
Figure 2
Figure 2
Representative scheme of the IVT mRNA structure and its principal modifications to improve the efficacy and the stability, and to reduce the immunogenicity.
Figure 3
Figure 3
Representative scheme of chemical nanocarriers for mRNA delivery.
Figure 4
Figure 4
Representative scheme of the difference between non-replicating mRNA-based vaccines and self-amplifying mRNA (SAM) vaccines.
Figure 5
Figure 5
Representative scheme of cellular transdifferentiation and cellular reprogramming therapies.
See this image and copyright information in PMC

References

    1. European Medicines Agency Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products. Eur. Med. Agency Guidel. 2015;44:1–41.
    1. del Pozo-Rodríguez A., Rodríguez-Gascón A., Rodríguez-Castejón J., Vicente-Pascual M., Gómez-Aguado I., Battaglia L.S., Solinís M.A. Gene therapy. Adv. Biochem. Eng. Biotechnol. 2019;171:321–368. - PubMed
    1. Thorne B., Takeya R., Vitelli F., Swanson X. Gene Therapy. In: Kiss B., Gottschalk U., Pohlscheidt M., editors. New Bioprocessing Strategies: Development and Manufacturing of Recombinant Antibodies and Proteins. Advances in Biochemical Engineering/Biotechnology. Volume 165 Springer; Cham, Switzerland: 2017.
    1. Anguela X.M., High K.A. Entering the Modern Era of Gene Therapy. Ann. Rev. Med. 2019;70:273–288. doi: 10.1146/annurev-med-012017-043332. - DOI - PubMed
    1. Hajj K.A., Whitehead K.A. Tools for translation: Non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2017;2:17056. doi: 10.1038/natrevmats.2017.56. - DOI

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