Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Open accessAbstract
Lipid nanoparticle (LNP) formulated messenger RNA-based (LNP-mRNA) vaccines came into the spotlight as the first vaccines against SARS-CoV-2 virus to be applied worldwide. Long-known benefits of mRNA-based technologies consisting of relatively simple and fast engineering of mRNA encoding for antigens and proteins of interest, no genomic integration, and fast and efficient manufacturing process compared with other biologics have been verified, thus establishing a basis for a broad range of applications. The intrinsic immunogenicity of LNP formulated in vitro transcribed (IVT) mRNA is beneficial to the LNP-mRNA vaccines. However, avoiding immune activation is critical for therapeutic applications of LNP-mRNA for protein replacement where targeted mRNA expression and repetitive administration of high doses for a lifetime are required. This review summarizes our current understanding of immune activation induced by mRNA, IVT byproducts, and LNP. It gives a comprehensive overview of the present status of preclinical and clinical studies in which LNP-mRNA is used for protein replacement and treatment of rare diseases with an emphasis on safety. Moreover, the review outlines innovations and strategies to advance pharmacology and safety of LNP-mRNA for non-immunotherapy applications.
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Tenchov, R., Bird, R., Curtze, A. E., & Zhou, Q. (2021) · ACS Nano · doi:10.1021/acsnano.1c04996 · Cited by 2,221 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
Szabó, G. T., Mahiny, A. J., & Vlatkovic, I. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.016 · Cited by 308 · see citing works
Self-citationSittplangkoon, C., Alameh, M.-G., Weissman, D., Lin, P. J. C., Tam, Y. K., Prompetchara, E., & Palaga, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.983000 · Cited by 79 · see citing works
- Authors
- Vlatkovic, I.
- Affiliations
- BioNTech (Germany) (DE)
- Corresponding author
- Vlatkovic, Irena
- ORCID
- Vlatkovic, Irena
- Venue
- Biomedicines
- Publisher
- MDPI AG
- Published
- 2021-05-10
- Volume
- 9
- Issue
- 5
- Pages
- 530
- ISSN
- 2227-9059 (ISSN-L)
- PMC
- PMC8151051
- OpenAlex
- W3163563420
- Cited by
- 112
- References
- 165
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 23 · 2023: 28 · 2022: 17 · 2021: 4
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA therapeutics, in vitro transcribed mRNA, immune activation, rare diseases, protein replacement therapy, mRNA vaccines, SARS-CoV-2, safety
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