The DOI matches its Crossref record; 181 of the 184 references it cites were found in a registry or an index.
Opportunities and Challenges in the Delivery of mRNA-Based Vaccines
Open accessAbstract
In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine.
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“At present, the 3′ UTR is mainly derived from hemoglobin subunit α (HBA) and subunit β (HBB) genes,140 but it can also be derived from albumin (ALB), heat-shock protein 70 (Hsp70), tyrosine hydroxylase (TH), and collagen alpha 1 (COL1A1) genes.141–143”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [140]
In the citing paper
“Further, the 5′ cap protects the mRNA sterically from degradation by exonucleases, and it works synergistically with the poly(A) tail at the 3′ end, poly(A) binding proteins and translation initiation factor proteins to circularize mRNA and recruit ribosomes for initiating translation10,11.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [10]
In the citing paper
“As in mammals, the first or second nucleotide from the 5′ end is methylated on the 2′ hydroxyl of the ribose (2′-O-methylation), which prevents recognition by cytosolic sensors of viral RNA10, and hence prevents unintended immune responses.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [10]
In the citing paper
“The 5′ and 3′ UTRs flanking the coding region regulate mRNA translation, half-life and subcellular localization10,14.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [10]
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Metadata
- Authors
- Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C., & Thakur, A.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Thakur, Aneesh
- Venue
- Pharmaceutics
- Publisher
- MDPI AG
- Published
- 2020-01-28
- Volume
- 12
- Issue
- 2
- Pages
- 102
- ISSN
- 1999-4923 (ISSN-L)
- PMC
- PMC7076378
- OpenAlex
- W3004416358
- Cited by
- 584
- References
- 184
- Citations by year
- 2026: 55 · 2025: 110 · 2024: 90 · 2023: 109 · 2022: 125 · 2021: 76 · 2020: 19
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Pharmaceutics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Det Frie Forskningsråd (9041-00198B)
- 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 vaccines, mRNA delivery, mRNA stability, nucleic acid degradation, immune activation, clinical translation, cancer immunotherapy, genetic disease treatment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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