The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Delivery of modified mRNA to damaged myocardium by systemic administration of lipid nanoparticles
Open accessAbstract
Lipid Nanoparticles (LNPs) are a promising drug delivery vehicle for clinical siRNA delivery. Modified mRNA (modRNA) has recently gained great attention as a therapeutic molecule in cardiac regeneration. However, for mRNA to be functional, it must first reach the diseased myocardium, enter the target cell, escape from the endosomal compartment into the cytosol and be translated into a functional protein. However, it is unknown if LNPs can effectively deliver mRNA, which is much larger than siRNA, to the ischemic myocardium. Here, we evaluated the ability of LNPs to deliver mRNA to the myocardium upon ischemia-reperfusion injury functionally. By exploring the bio-distribution of fluorescently labeled LNPs, we observed that, upon reperfusion, LNPs accumulated in the infarct area of the heart. Subsequently, the functional delivery of modRNA was evaluated by the administration of firefly luciferase encoding modRNA. Concomitantly, a significant increase in firefly luciferase expression was observed in the heart upon myocardial reperfusion when compared to sham-operated animals. To characterize the targeted cells within the myocardium, we injected LNPs loaded with Cre modRNA into Cre-reporter mice. Upon LNP infusion, Tdtomato+ cells, derived from Cre mediated recombination, were observed in the infarct region as well as the epicardial layer upon LNP infusion. Within the infarct area, most targeted cells were cardiac fibroblasts but also some cardiomyocytes and macrophages were found. Although the expression levels were low compared to LNP-modRNA delivery into the liver, our data show the ability of LNPs to functionally deliver modRNA therapeutics to the damaged myocardium, which holds great promise for modRNA-based cardiac therapies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Similar to RNP electroporation, Cas9 mRNA and sgRNA can also be delivered into cells via electroporation or liposome-based vectors (Evers et al., 2022; Yu et al., 2023) to improved genome editing fidelity.”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Evers et al., 2022
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure
Yancy, C. W., Jessup, M. L., Bozkurt, B., Butler, J., Casey, D. E., Colvin, M. M., Drazner, M. H., Filippatos, G. S., Fonarow, G. C., Givertz, M. M., et al. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.04.025 · Cited by 3,532
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662
Progress and problems with the use of viral vectors for gene therapy
Thomas, C. E., Ehrhardt, A., & Kay, M. A. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1066 · Cited by 2,501
Karikó, K., Muramatsu, H., Welsh, F. A., Ludwig, J., Kato, H., Akira, S., & Weissman, D. (2008) · Molecular Therapy · doi:10.1038/mt.2008.200 · Cited by 1,930
In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes
Li, Q., Huang, Y., Spencer, C. I., Foley, A., Vedantham, V., Liu, L., Conway, S. J., Fu, J., & Srivastava, D. (2012) · Nature · doi:10.1038/nature11044 · Cited by 1,376
Laflamme, M. A., & Murry, C. E. (2011) · Nature · doi:10.1038/nature10147 · Cited by 1,272
Heart repair by reprogramming non-myocytes with cardiac transcription factors
Song, K., Nam, Y., Luo, X., Qi, X., Tan, W. H., Huang, G. N., Acharya, A., Smith, C. L., Tallquist, M. D., Neilson, E. G., et al. (2012) · Nature · doi:10.1038/nature11139 · Cited by 1,162
Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury
Bersell, K. R., Arab, S., Haring, B., & Kühn, B. (2009) · Cell · doi:10.1016/j.cell.2009.04.060 · Cited by 1,053
Pardi, N., Tuyishime, S., Muramatsu, H., Kariko, K., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., & Weissman, D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.007 · Cited by 1,014
Karikó, K., Muramatsu, H., Ludwig, J., & Weissman, D. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr695 · Cited by 898
Research works printed but not linked: 1
- de Wit, 2020, Cellular and molecular mechanism of cardiac regeneration: a comparison of newts, Zebrafish Mammals Biomol., 10
Cited by
Sorted by citations
Items 101–113 of 113
Myocardial infarction creates a critical time window for AAV gene therapyPreprint
Chen, G., Zhang, Y., Chen, Z., Yang, L., Gao, F., Dong, E., & Guo, Y. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.10.597311
Myocardial infarction creates a critical time window for AAV-based cardiac gene transferPreprint
Guo, Y., Chen, G., Zhang, Y., Liu, Z., Chen, Z., Yang, L., Gao, F., & Dong, E. (2024) · Research Square · doi:10.21203/rs.3.rs-5291943/v1
Drug delivery to the myocardium
(2025) · Elsevier eBooks · doi:10.1016/b978-0-443-26787-1.00011-4
Harnessing extracellular vesicles to deliver genetic medicine for cardiac repair
Xie, S., Ilahibaks, N. F., Lei, Z., & Sluijter, J. P. G. (2025) · Nanomedicine · doi:10.1080/17435889.2025.2500913
Self-citationAvenues for Optimization of Cardiac Therapeutics for Minimally Invasive DeliveryPreprint
Li, Y., Vunjak‐Novakovic, G., & Cheng, K. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5394552
Nanoparticle-Mediated Delivery of Materials for Effective Regeneration
Shrestha, A., Haque, M. A., & Mattheolabakis, G. (2025) · Springer eBooks · doi:10.1007/978-3-031-93677-7_17
Bergada, C. B., Song, P., Knudsen, K. B., Jaynes, C. L., Leuvenink, H. G. D., Llorente, V. R., van Furth, L. A., Hager, H., Nørregaard, R., Hillebrands, J., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.28.672793
PDE3A2 modRNA Fine-Tunes Nuclear cAMP Microdomains and Reverses Pathological Cardiac HypertrophyPreprint
Xiang, W., Lian, M., Guan, Q., Sun, X., Li, S., Lu, H., Qin, G., Xiang, Y. K., Ni, H., & Wang, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.30.679675
Shadab, A., Ahmad, U., Choonara, Y. E., & Faiyazuddin, M. (2026) · ACS Materials Au · doi:10.1021/acsmaterialsau.6c00068
Zaman, W., & Ayaz, A. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146467
Ischemic myocardium-targeted NAD+ nanotherapy mitigates myocardial ischemia/reperfusion injury
Xie, X., Zhang, X., Zhou, Z., Han, C., Zeng, K., Wang, L., Chen, J., Zhang, Y., Zhang, Y., & Ye, M. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115454
Regenerative Strategies for Myocardial Infarction and Their Present Clinical Application
Cruz, J. M. C., Nevado, J. B., Lozano-Gerona, J., Manua, A. J., Agsaoay, M. L. J. S., Pedro, J. V. B. S., Ledesma, D. J. T., Manangan, A. B. G., & Mazahery, A. R. (2026) · Rejuvenation Research · doi:10.1177/15491684261496118
Ahmadi, A., Refaat, A., Miao, K., Vidallon, M. L. P., McFadyen, J. D., Wang, X., & Peter, K. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115980
Metadata
- Authors
- Evers, M. J. W., Du, W., Yang, Q., Kooijmans, S. A. A., Vink, A., van Steenbergen, M., Vader, P., de Jager, S. C. A., Fuchs, S. A., Mastrobattista, E., Sluijter, J. P. G., Lei, Z., & Schiffelers, R.
- Affiliations
- University Medical Center Utrecht (NL)
- Harbin Medical University (CN)
- Utrecht University (NL)
- Corresponding author
- Schiffelers, Raymond
- ORCID
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2022-03
- Volume
- 343
- Pages
- 207-216
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W4206915884
- Cited by
- 113
- References
- 48
- Citations by year
- 2026: 19 · 2025: 44 · 2024: 23 · 2023: 20 · 2022: 7
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- European Commission (HORIZON2020, 721058, 725229, 825828)
- ZonMw (725229, 116002016)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (16169)
- Ministerie van Economische Zaken, Landbouw en Innovatie
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- lipid nanoparticles, modified mRNA, myocardial ischemia-reperfusion injury, cardiac regeneration, systemic drug delivery, firefly luciferase reporter, Cre reporter mice, cardiac fibroblasts
- MeSH terms
- Animals, Infarction, Liposomes, Myocardium, RNA, Messenger, RNA, Small Interfering, Luciferases, Firefly, Mice, Nanoparticles
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 ›
Are you an author, or do you see a problem with this page? Request a review
