Cited by 13RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems
Deciphering the biological fate of mRNA-LNP-based biologics: A perspective from tissue to intracellular distribution
Open accessXu, Xin, Cui, Lili, Zhang, Yong, Gu, Jingkai·2026·Acta Pharmaceutica Sinica B
Abstract
The remarkable clinical success of mRNA-lipid nanoparticle (mRNA-LNP) vaccines, particularly evidenced by their pandemic-era impact and subsequent 2023 Nobel Prize recognition, has intensified global efforts to expand their application toward therapeutic biologics. Despite showing strong preventive effects, there are still fundamental knowledge gaps in comprehensively defining the hierarchical biological trajectory of mRNA-LNP formulations, which spans from initial systemic exposure, tissue-specific biodistribution, and intracellular delivery to ultimate protein expression dynamics. These unresolved mechanistic questions pose significant constraints on the rational design of next-generation mRNA-LNP therapeutics, which face increased demands for precision dosing, therapeutic efficacy optimization, and enhanced safety profiles. This review discusses the in vivo fate of mRNA-LNP, focusing specifically on blood/tissue/cellular distribution and kinetics/exposure profiles of both intact mRNA-LNP and dissociated components post-administration. It discusses key factors influencing the distribution of expressed protein and summarizes the corresponding research toolkits along with their advantages and disadvantages. Additionally, it compiles strategies to enhance delivery efficacy, tissue tropism, and safety profiles of mRNA-LNP. We anticipate a better understanding of the biological processes and dynamic pattern of mRNA-LNP, which will accelerate the development of next-generation mRNA biologics with predictable safety and delivery efficiency. Systematically characterizing the biological fate of mRNA-LNPs, from initial systemic exposure to tissue-specific biodistribution and intracellular delivery, and ultimately to protein expression dynamics, may benefit the rational development of next-generation mRNA-LNP therapeutics.
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Variations in reporter protein accumulation within tissues may also be influenced by other factors, including differences in elongation rates, physicochemical properties of LNPs, and kinetics of endosomal escape into cytosol.
“Variations in reporter protein accumulation within tissues may also be influenced by other factors, including differences in elongation rates, the physicochemical properties of LNPs, and the kinetics of endosomal escape into the cytosol [33].”
From Identification of novel 5’ UTR variants for enhanced mRNA translation and vaccine immunogenicity (2026) · cites this paper as [33]
The section on factors influencing expressed-protein distribution links tissue-level differences to LNP physicochemical properties and tissue-specific translational efficiency. The endosomal-escape section links escape efficiency to protein expression, but our copy does not identify differences in elongation rates as a cause of reporter-protein accumulation or establish that endosomal-escape kinetics explain variation between tissues. No page numbers are available in the indexed passages. (LLM, conf=0.85)
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200 of 248 shown
Cited by
Sorted by citations
Identification of novel 5’ UTR variants for enhanced mRNA translation and vaccine immunogenicity
Mazunina, E. P., Dzharullaeva, A. S., Kleymenov, D. A., Bykonia, E. N., Kozlova, S. R., Usachev, E. V., Panova, E. A., Konopleva, M. V., Telegina, D. V., Kukushkina-Zvezdova, A. A., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-59586-5
- Authors
- Xu, X., Cui, L., Zhang, Y., & Gu, J.
- Affiliations
- Jilin University (CN)
- CSPC Pharmaceutical Group (CN)
- Corresponding author
- Zhang, Yong
- Gu, Jingkai
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2026-04
- Volume
- 16
- Issue
- 4
- Pages
- 1943-1970
- ISSN
- 2211-3835 (ISSN-L)
- PMC
- PMC13104687
- OpenAlex
- W4416421418
- Cited by
- 13
- References
- 22
- Citations by year
- 2026: 13
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82030107, 82373944)
- 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 › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- mRNA lipid nanoparticles, mRNA therapeutics, tissue distribution, intracellular delivery, protein expression dynamics, tissue tropism, treatment safety, mRNA vaccines
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