Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction
Open accessAbstract
In a cell-free approach to regenerative therapeutics, transient application of paracrine factors in vivo could be used to alter the behavior and fate of progenitor cells to achieve sustained clinical benefits. Here we show that intramyocardial injection of synthetic modified RNA (modRNA) encoding human vascular endothelial growth factor-A (VEGF-A) results in the expansion and directed differentiation of endogenous heart progenitors in a mouse myocardial infarction model. VEGF-A modRNA markedly improved heart function and enhanced long-term survival of recipients. This improvement was in part due to mobilization of epicardial progenitor cells and redirection of their differentiation toward cardiovascular cell types. Direct in vivo comparison with DNA vectors and temporal control with VEGF inhibitors revealed the greatly increased efficacy of pulse-like delivery of VEGF-A. Our results suggest that modRNA is a versatile approach for expressing paracrine factors as cell fate switches to control progenitor cell fate and thereby enhance long-term organ repair.
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
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?
Conclusive data have also been presented for mRNA as a platform for protein (replacement) therapies.
“Conclusive data have also been presented for mRNA as a platform for protein (replacement) therapies (Kormann et al, 2011; Kariko et al, 2012; Zangi et al, 2013; Thess et al, 2015; Balmayor et al, 2016).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Zangi et al, 2013
The Abstract and Results report that VEGF-A modRNA produced a therapeutic protein and improved cardiac outcomes in a mouse model of myocardial infarction. This supports mRNA as a potential platform for protein-based therapy, but the paper does not demonstrate protein replacement therapy specifically or establish conclusive efficacy across such therapies. Page numbers were not supplied in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredConventional unmodified mRNAs are inferior to molecules harboring specific nucleoside modifications, but the picture changes dramatically with sophisticated sequence-engineering.
“Our work principally confirms that conventional unmodified mRNAs are inferior to molecules harboring specific nucleoside modifications as suggested by various recent reports,23,24,25,26,27 however, the picture changes dramatically with a sophisticated sequence-engineering.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [25]
Intramyocardial injection of mRNA expressing human VEGF-A with RNAiMAX decreased morbidity of mice with myocardial infarction following repair of heart function.
“For example, an intramyocardial injection of mRNA expressing human vascular endothelial growth factor A (VEGF-A) with RNAiMAX decreased the morbidity of mice with myocardial infarction following the repair of heart function.[201]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [201]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237 · see citing works
A global double-fluorescent Cre reporter mouse
Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L., & Luo, L. (2007) · genesis · doi:10.1002/dvg.20335 · Cited by 3,491 · see citing works
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728 · see citing works
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 · see citing works
Self-citationKarikó, 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 · see citing works
Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages
Laugwitz, K., Moretti, A., Lam, J. T., Gruber, P. J., Chen, Y., Woodard, S., Lin, L.-Z., Cai, C., Lu, M. M., Reth, M. G., et al. (2005) · Nature · doi:10.1038/nature03215 · Cited by 1,302 · see citing works
Self-citationVEGF-Induced Adult Neovascularization: Recruitment, Retention, and Role of Accessory Cells
Grunewald, M., Avraham, I., Dor, Y., Bachar-Lustig, E., Itin, A., Yung, S., Chimenti, S., Landsman, L., Abramovitch, R., & Keshet, E. (2006) · Cell · doi:10.1016/j.cell.2005.10.036 · Cited by 1,125 · see citing works
Moretti, A., Caron, L., Nakano, A., Lam, J. T., Bernshausen, A., Chen, Y., Qyang, Y., Bu, L., Sasaki, M., Martı́n-Puig, S., et al. (2006) · Cell · doi:10.1016/j.cell.2006.10.029 · Cited by 1,037 · see citing works
Self-citationEpicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
Zhou, B., Ma, Q., Rajagopal, S., Wu, S. M., Domian, I., Rivera-Feliciano, J., Jiang, D., von Gise, A., Ikeda, S., Chien, K. R., et al. (2008) · Nature · doi:10.1038/nature07060 · Cited by 1,019 · see citing works
Self-citationRecognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response
Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2005.12.003 · Cited by 1,003 · see citing works
A myocardial lineage derives from Tbx18 epicardial cells
Cai, C., Martin, J., Sun, Y., Cui, L., Wang, L., Ouyang, K., Yang, L., Bu, L., Liang, X., Zhang, X., et al. (2008) · Nature · doi:10.1038/nature06969 · Cited by 783 · see citing works
Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
Kormann, M. S. D., Hasenpusch, G., Aneja, M. K., Nica, G., Flemmer, A. W., Herber-Jonat, S., Huppmann, M., Mays, L. E., Illenyi, M., Schams, A., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1733 · Cited by 733 · see citing works
VEGF Gene Delivery to Myocardium
Lee, R. J., Springer, M. L., Blanco-Bose, W. E., Shaw, R. M., Ursell, P. C., & Blau, H. M. (2000) · Circulation · doi:10.1161/01.cir.102.8.898 · Cited by 696 · see citing works
De novo cardiomyocytes from within the activated adult heart after injury
Smart, N., Bollini, S., Dubé, K. N., Vieira, J. M., Zhou, B., Davidson, S. M., Yellon, D. M., Riegler, J., Price, A. N., Lythgoe, M. F., et al. (2011) · Nature · doi:10.1038/nature10188 · Cited by 632 · see citing works
Self-citationNoyan-Ashraf, M. H., Momen, M. A., Ban, K., Sadi, A.-M., Zhou, Y.-Q., Riazi, A. M., Baggio, L. L., Henkelman, R. M., Husain, M., & Drucker, D. J. (2009) · Diabetes · doi:10.2337/db08-1193 · Cited by 575 · see citing works
Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages
Bu, L., Jiang, X. M., Martı́n-Puig, S., Caron, L., Zhu, S., Shao, Y., Roberts, D. J., Huang, P. L., Domian, I. J., & Chien, K. R. (2009) · Nature · doi:10.1038/nature08191 · Cited by 551 · see citing works
Self-citationAdult mouse epicardium modulates myocardial injury by secreting paracrine factors
Zhou, B., Honor, L. B., He, H., Ma, Q., Oh, J., Butterfield, C., Lin, R., Melero‐Martin, J. M., Dolmatova, E. V., Duffy, H. S., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45529 · Cited by 509 · see citing works
Self-citationIsolation of Adult Mouse Myogenic Progenitors
Sherwood, R. I., Christensen, J. L., Conboy, I. M., Conboy, M. J., Rando, T. A., Weissman, I. L., & Wagers, A. J. (2004) · Cell · doi:10.1016/j.cell.2004.10.021 · Cited by 491 · see citing works
Self-citationHighly Efficient, Functional Engraftment of Skeletal Muscle Stem Cells in Dystrophic Muscles
Cerletti, M., Jurga, S., Witczak, C. A., Hirshman, M. F., Shadrach, J. L., Goodyear, L. J., & Wagers, A. J. (2008) · Cell · doi:10.1016/j.cell.2008.05.049 · Cited by 472 · see citing works
Self-citationSpilsbury, K., Garrett, K. L., Shen, W.-Y., Constable, I. J., & Rakoczy, P. E. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64525-7 · Cited by 395 · see citing works
Zhou, J., Tan, S.-H., Nicolas, V., Bauvy, C., Yang, N., Zhang, J., Xue, Y., Codogno, P., & Shen, H. (2013) · Cell Research · doi:10.1038/cr.2013.11 · Cited by 391 · see citing works
Dor, Y., Djonov, V., Abramovitch, R., Itin, A., Fishman, G. I., Carmeliet, P., Goelman, G., & Keshet, E. (2002) · The EMBO Journal · doi:10.1093/emboj/21.8.1939 · Cited by 389 · see citing works
Adult Cardiac-Resident MSC-like Stem Cells with a Proepicardial Origin
Chong, J. J. H., Chandrakanthan, V., Xaymardan, M., Asli, N. S., Li, J., Ahmed, I. M., Heffernan, C., Menon, M. K., Scarlett, C. J., Rashidianfar, A., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.10.002 · Cited by 386 · see citing works
Self-citationLoffredo, F. S., Steinhauser, M. L., Gannon, J., & Lee, R. T. (2011) · Cell stem cell · doi:10.1016/j.stem.2011.02.002 · Cited by 381 · see citing works
Hoshijima, M., Ikeda, Y., Iwanaga, Y., Minamisawa, S., Date, M., Gu, Y., Iwatate, M., Li, M., Wang, L., Wilson, J. M., et al. (2002) · Nature Medicine · doi:10.1038/nm739 · Cited by 372 · see citing works
Self-citationCardiac Stem Cell Therapy and the Promise of Heart Regeneration
Garbern, J. C., & Lee, R. T. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.05.008 · Cited by 367 · see citing works
Distinct Compartments of the Proepicardial Organ Give Rise to Coronary Vascular Endothelial Cells
Katz, T. C., Singh, M. K., Degenhardt, K. R., Rivera‐Feliciano, J., Johnson, R. L., Epstein, J. A., & Tabin, C. J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.01.012 · Cited by 352 · see citing works
PET/MRI of Inflammation in Myocardial Infarction
Lee, W. W., Marinelli, B. S., van der Laan, A. M., Sena, B. F., Gorbatov, R., Leuschner, F., Dutta, P., Iwamoto, Y., Ueno, T., Begieneman, M. P. V., et al. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.08.066 · Cited by 336 · see citing works
Self-citationThe serosal mesothelium is a major source of smooth muscle cells of the gut vasculature
Wilm, B., Ipenberg, A., Hastie, N., Burch, J., & Bader, D. (2005) · Development · doi:10.1242/dev.02141 · Cited by 328 · see citing works
Tarnavski, O., McMullen, J. R., Schinke, M., Nie, Q. H., Kong, S. W., & Izumo, S. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00041.2003 · Cited by 318 · see citing works
Takagawa, J., Zhang, Y., Wong, M. L., Sievers, R. E., Kapasi, N. K., Wang, Y., Yeghiazarians, Y., Lee, R. J., Grossman, W., & Springer, M. L. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00033.2007 · Cited by 310 · see citing works
Qyang, Y., Martı́n-Puig, S., Chiravuri, M., Chen, S., Xu, H., Bu, L., Jiang, X., Lin, L., Granger, A., Moretti, A., et al. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.05.018 · Cited by 309 · see citing works
Self-citationMalliaras, K. G., Zhang, Y., Seinfeld, J., Galang, G., Tseliou, E., Cheng, K., Sun, B., Aminzadeh, M. A., & Marbán, E. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201201737 · Cited by 286 · see citing works
Karikó, K., Muramatsu, H., Keller, J. M., & Weissman, D. (2012) · Molecular Therapy · doi:10.1038/mt.2012.7 · Cited by 282 · see citing works
Tbx18 and the fate of epicardial progenitors
Christoffels, V. M., Grieskamp, T., Norden, J., Mommersteeg, M. T. M., Rudat, C., & Kispert, A. (2009) · Nature · doi:10.1038/nature07916 · Cited by 273 · see citing works
Eppler, S. M., Combs, D. L., Henry, T. D., López, J. J., Ellis, S. G., Yi, J., Annex, B. H., McCluskey, E. R., & Zioncheck, T. F. (2002) · Clinical Pharmacology & Therapeutics · doi:10.1067/mcp.2002.126179 · Cited by 267 · see citing works
Sauvé, M., Ban, K., Momen, M. A., Zhou, Y., Henkelman, R. M., Husain, M., & Drucker, D. J. (2010) · Diabetes · doi:10.2337/db09-0955 · Cited by 264 · see citing works
Wessels, A., van den Hoff, M. J. B., Adamo, R. F., Phelps, A. L., Lockhart, M. M., Sauls, K., Briggs, L. E., Norris, R. A., van Wijk, B., Perez-Pomares, J. M., et al. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.04.020 · Cited by 263 · see citing works
von Gise, A., Zhou, B., Honor, L. B., Ma, Q., Petryk, A., & Pu, W. T. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.05.668 · Cited by 252 · see citing works
Self-citationTowards regenerative therapy for cardiac disease
Ptaszek, L. M., Mansour, M., Ruskin, J. N., & Chien, K. R. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60075-0 · Cited by 242 · see citing works
Self-citationShen, B., Lee, D. Y., Gerber, H., Keyt, B. A., Ferrara, N., & Zioncheck, T. F. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.45.29979 · Cited by 211 · see citing works
Generation of Functional Ventricular Heart Muscle from Mouse Ventricular Progenitor Cells
Domian, I. J., Chiravuri, M., van der Meer, P., Feinberg, A. W., Shi, X., Shao, Y., Wu, S. M., Parker, K. K., & Chien, K. R. (2009) · Science · doi:10.1126/science.1177350 · Cited by 208 · see citing works
Self-citationSvensson, E. C., Marshall, D. J., Woodard, K., Lin, H., Jiang, F., Chu, L., & Leiden, J. M. (1999) · Circulation · doi:10.1161/01.cir.99.2.201 · Cited by 206 · see citing works
Kruithof, B. P. T., van Wijk, B., Somi, S., Julio, M. K., Pérez-Pomares, J. M., Weesie, F., Wessels, A., Moorman, A. F. M., & van den Hoff, M. J. B. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.03.033 · Cited by 169 · see citing works
Choi, M. K., Wang, Z., Ban, T., Yanai, H., Lu, Y., Koshiba, R., Nakaima, Y., Hangai, S., Savitsky, D. A., Nakasato, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909545106 · Cited by 117 · see citing works
Modified Foxp3 mRNA protects against asthma through an IL-10-dependent mechanism
Mays, L. E., Ammon-Treiber, S., Mothes, B., Alkhaled, M., Rottenberger, J., Müller-Hermelink, E. S., Grimm, M., Mezger, M., Beer-Hammer, S., von Stebut, E., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci65351 · Cited by 113 · see citing works
Permeability properties of tumor surrogate blood vessels induced by VEGF-A
Nagy, J. A., Feng, D., Vasile, E., Wong, W. H., Shih, S., Dvořàk, A. M., & Dvorak, H. F. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700436 · Cited by 112 · see citing works
Lui, K. O., Zangi, L., Silva, E. A., Bu, L., Sahara, M., Li, R. A., Mooney, D. J., & Chien, K. R. (2013) · Cell Research · doi:10.1038/cr.2013.112 · Cited by 108 · see citing works
Self-citationGenetic Cre-loxP Assessment of Epicardial Cell Fate Using Wt1-Driven Cre Alleles
Zhou, B., & Pu, W. T. (2012) · Circulation Research · doi:10.1161/circresaha.112.275784 · Cited by 87 · see citing works
Self-citationComparison of Nonviral Transfection and Adeno-Associated Viral Transduction on Cardiomyocytes
Djurovic, S., Iversen, N., Jeansson, S. L., et al. (2004) · Molecular Biotechnology · doi:10.1385/mb:28:1:21 · Cited by 84 · see citing works
Tafuro, S., Ayuso, E., Zacchigna, S., Zentilin, L., Moimas, S., Dore, F., & Giacca, M. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp152 · Cited by 77 · see citing works
Xu, H., Månsson‐Broberg, A., Grinnemo, K., et al. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.011 · Cited by 62 · see citing works
Self-citationIsolation, Culture, and Functional Analysis of Adult Mouse Cardiomyocytes
Liao, R., & Jain, M. (2007) · Methods in molecular medicine · doi:10.1007/978-1-59745-571-8_16 · Cited by 60 · see citing works
Additive effect of AAV-mediated angiopoietin-1 and VEGF expression on the therapy of infarcted heart
Su, H. Y., Takagawa, J., Huang, Y., et al. (2008) · International Journal of Cardiology · doi:10.1016/j.ijcard.2007.12.034 · Cited by 41 · see citing works
Myocardial angiogenesis after chronic ghrelin treatment in a rat myocardial infarction model
Yuan, M., He-huang, Hu, H., et al. (2012) · Regulatory Peptides · doi:10.1016/j.regpep.2012.08.013 · Cited by 32 · see citing works
Therapeutic Myocardial Angiogenesis Via Vascular Endothelial Growth Factor Gene Therapy
Patterson, C., & Runge, M. S. (2000) · Circulation · doi:10.1161/01.cir.102.9.940 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
mRNA-based therapeutics--developing a new class of drugs
Sahin, U., Karikó, K., & Türeci, Ö. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4278 · Cited by 2,474 · see citing works
Zuris, J. A., Thompson, D. B., Shu, Y., Guilinger, J. P., Bessen, J. L., Hu, J. H., Maeder, M. L., Joung, J. K., Chen, Z.-Y., & Liu, D. R. (2015) · Nature Biotechnology · doi:10.1038/nbt.3081 · Cited by 1,460 · see citing works
Block copolymer micelles in nanomedicine applications
Cabral, H., Miyata, K., Osada, K., & Kataoka, K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00199 · Cited by 1,309 · see citing works
Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
Kowalski, P. S., Rudra, A., Miao, L., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.012 · Cited by 1,127 · see citing works
Wang, G., McCain, M. L., Yang, L., He, A., Pasqualini, F. S., Agarwal, A., Yuan, H., Jiang, D., Zhang, D., Zangi, L., et al. (2014) · Nature Medicine · doi:10.1038/nm.3545 · Cited by 837 · see citing works
Self-citationTools for translation: non-viral materials for therapeutic mRNA delivery
Hajj, K. A., & Whitehead, K. A. (2017) · Nature Reviews Materials · doi:10.1038/natrevmats.2017.56 · Cited by 799 · see citing works
Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA
Long, C., McAnally, J. R., Shelton, J. M., Mireault, A. A., Bassel-Duby, R., & Olson, E. N. (2014) · Science · doi:10.1126/science.1254445 · Cited by 720 · see citing works
Andries, O., Mc Cafferty, S., De Smedt, S. C., Weiss, R., Sanders, N. N., & Kitada, T. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.051 · Cited by 701 · see citing works
Advances in the delivery of RNA therapeutics: from concept to clinical reality
Kaczmarek, J. C., Kowalski, P. S., & Anderson, D. G. (2017) · Genome Medicine · doi:10.1186/s13073-017-0450-0 · Cited by 656 · see citing works
Yanez Arteta, M., Kjellman, T., Bartesaghi, S., Wallin, S., Wu, X., Kvist, A. J., Dabkowska, A., Székely, N., Radulescu, A., Bergenholtz, J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1720542115 · Cited by 534 · see citing works
Thess, A., Grund, S., Mui, B. L., Hope, M. J., Baumhof, P., Fotin-Mleczek, M., & Schlake, T. (2015) · Molecular Therapy · doi:10.1038/mt.2015.103 · Cited by 513 · see citing works
The challenge and prospect of mRNA therapeutics landscape
Weng, Y., Li, C., Yang, T., Hu, B., Zhang, M., Guo, S., Xiao, H., Liang, X.-J., & Huang, Y. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107534 · Cited by 417 · see citing works
Liang, F., Lindgren, G., Lin, A., Thompson, E. A., Ols, S., Röhss, J., John, S., Hassett, K., Yuzhakov, O., Bahl, K., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.08.006 · Cited by 395 · see citing works
Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems
Guan, S., & Rosenecker, J. (2017) · Gene Therapy · doi:10.1038/gt.2017.5 · Cited by 389 · see citing works
Pardi, N., Secreto, A. J., Shan, X., Debonera, F., Glover, J., Yi, Y., Muramatsu, H., Ni, H., Mui, B. L., Tam, Y. K., et al. (2017) · Nature Communications · doi:10.1038/ncomms14630 · Cited by 352 · see citing works
Systemic delivery of factor IX messenger RNA for protein replacement therapy
Ramaswamy, S., Tonnu, N., Tachikawa, K., Limphong, P., Vega, J. B., Karmali, P. P., Chivukula, P., & Verma, I. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1619653114 · Cited by 301 · see citing works
Svitkin, Y. V., Cheng, Y. M., Chakraborty, T., Presnyak, V., John, M., & Sonenberg, N. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx135 · Cited by 278 · see citing works
mRNA Delivery for Therapeutic Anti-HER2 Antibody Expression In Vivo
Rybakova, Y., Kowalski, P. S., Huang, Y., Gonzalez, J. T., Heartlein, M. W., DeRosa, F., Delcassian, D., & Anderson, D. G. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.05.012 · Cited by 218 · see citing works
Kwon, H., Kim, M., Seo, Y., Moon, Y. S., Lee, H. J., Lee, K., & Lee, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2017.11.034 · Cited by 208 · see citing works
The Role of the Epicardium During Heart Development and Repair
Quijada, P., Trembley, M. A., & Small, E. M. (2020) · Circulation Research · doi:10.1161/circresaha.119.315857 · Cited by 201 · see citing works
Sedic, M., Senn, J. J., Lynn, A., Laska, M., Smith, M., Platz, S. J., Bolen, J., Hoge, S., Bulychev, A., Jacquinet, E., et al. (2018) · Veterinary Pathology · doi:10.1177/0300985817738095 · Cited by 195 · see citing works
Biomaterials for mRNA delivery
Islam, M. A., Reesor, E. K. G., Xu, Y., Zope, H. R., Zetter, B. R., & Shi, J. (2015) · Biomaterials Science · doi:10.1039/c5bm00198f · Cited by 176 · see citing works
mRNA-Based Protein Replacement Therapy for the Heart
Magadum, A., Kaur, K., & Zangi, L. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.11.018 · Cited by 176 · see citing works
Self-citationmRNA mediates passive vaccination against infectious agents, toxins, and tumors
Thran, M., Mukherjee, J., Pönisch, M., Fiedler, K., Thess, A., Mui, B. L., Hope, M. J., Tam, Y. K., Horscroft, N., Heidenreich, R., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707678 · Cited by 166 · see citing works
“Conclusive data have also been presented for mRNA as a platform for protein (replacement) therapies (Kormann et al, 2011; Kariko et al, 2012; Zangi et al, 2013; Thess et al, 2015; Balmayor et al, 2016).”
BackgroundTherapeutic efficacy in a hemophilia B model using a biosynthetic mRNA liver depot system
DeRosa, F., Guild, B., Karve, S., Smith, L., Love, K., Dorkin, J. R., Kauffman, K. J., Zhang, J., Yahalom, B., Anderson, D. G., et al. (2016) · Gene Therapy · doi:10.1038/gt.2016.46 · Cited by 159 · see citing works
Minnaert, A.-K., Vanluchene, H., Verbeke, R., Lentacker, I., De Smedt, S. C., Raemdonck, K., Sanders, N. N., & Remaut, K. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.113900 · Cited by 157 · see citing works
Gene therapy for the treatment of heart failure: promise postponed
Hulot, J.-S., Ishikawa, K., & Hajjar, R. J. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw019 · Cited by 150 · see citing works
Später, D., Hansson, E. M., Zangi, L., & Chien, K. R. (2014) · Development · doi:10.1242/dev.091538 · Cited by 143 · see citing works
Self-citationExosome-mediated mRNA delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity
Tsai, S. J., Atai, N. A., Cacciottolo, M., Nice, J., Salehi, A., Guo, C., Sedgwick, A., Kanagavelu, S., & Gould, S. J. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101266 · Cited by 142 · see citing works
Nabhan, J. F., Wood, K. M., Rao, V. P., Morin, J., Bhamidipaty, S., LaBranche, T. P., Gooch, R. L., Bozal, F., Bulawa, C. E., & Guild, B. C. (2016) · Scientific Reports · doi:10.1038/srep20019 · Cited by 140 · see citing works
Van der Jeught, K., De Koker, S., Bialkowski, L., Heirman, C., Tjok Joe, P., Perche, F., Maenhout, S., Bevers, S., Broos, K., Deswarte, K., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b00966 · Cited by 139 · see citing works
Nanomedicine-Based Approaches for mRNA Delivery
Uchida, S., Perche, F., Pichon, C., & Cabral, H. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00618 · Cited by 139 · see citing works
Nanoplatforms for mRNA Therapeutics
Meng, C., Chen, Z., Li, G., Welte, T., & Shen, H. (2021) · Advanced Therapeutics · doi:10.1002/adtp.202000099 · Cited by 130 · see citing works
Biomedical applications of mRNA nanomedicine
Xiong, Q., Lee, G. Y., Ding, J., Li, W., & Shi, J. (2018) · Nano Research · doi:10.1007/s12274-018-2146-1 · Cited by 125 · see citing works
Delivery of mRNA Therapeutics for the Treatment of Hepatic Diseases
Trepotec, Z., Lichtenegger, E., Plank, C., Aneja, M. K., & Rudolph, C. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.12.012 · Cited by 115 · see citing works
Delivery of modified mRNA to damaged myocardium by systemic administration of lipid nanoparticles
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., et al. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.01.027 · Cited by 113 · see citing works
DeRosa, F., Smith, L., Shen, Y., Huang, Y., Pan, J., Xie, H., Yahalom, B., & Heartlein, M. W. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.001 · Cited by 111 · see citing works
Systemic mRNA delivery to the lungs by functional polyester-based carriers
Yan, Y., Xiong, H., Zhang, X., Cheng, Q., & Siegwart, D. J. (2017) · Biomacromolecules · doi:10.1021/acs.biomac.7b01356 · Cited by 111 · see citing works
Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
Devoldere, J., Dewitte, H., De Smedt, S. C., & Remaut, K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2015.07.009 · Cited by 112 · see citing works
Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles
Baba, M., Itaka, K., Kondo, K., Yamasoba, T., & Kataoka, K. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.01.017 · Cited by 109 · see citing works
Recent Developments in mRNA-Based Protein Supplementation Therapy to Target Lung Diseases
Sahu, I., Haque, A. K. M. A., Weidensee, B., Weinmann, P., & Kormann, M. S. D. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.02.019 · Cited by 104 · see citing works
Synthetic modified messenger RNA for therapeutic applications
Gao, M., Zhang, Q., Feng, X.-H., & Liu, J. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.06.020 · Cited by 89 · see citing works
Golombek, S., Pilz, M., Steinle, H., Kochba, E., Levin, Y., Lunter, D., Schlensak, C., Wendel, H. P., & Avci-Adali, M. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.03.005 · Cited by 88 · see citing works
RNA delivery biomaterials for the treatment of genetic and rare diseases
Zhao, W., Hou, X., Vick, O. G., & Dong, Y. (2019) · Biomaterials · doi:10.1016/j.biomaterials.2019.119291 · Cited by 82 · see citing works
Molecular Therapies for Inherited Retinal Diseases—Current Standing, Opportunities and Challenges
Vázquez-Domínguez, I., Garanto, A., & Collin, R. W. J. (2019) · Genes · doi:10.3390/genes10090654 · Cited by 80 · see citing works
Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis
Haque, A. K. M. A., Dewerth, A., Antony, J. S., Riethmüller, J., Schweizer, G. R., Weinmann, P., Latifi, N., Yasar, H., Pedemonte, N., Sondo, E., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-34960-0 · Cited by 80 · see citing works
Viral and Synthetic RNA Vector Technologies and Applications
Schott, J. W., Morgan, M., Galla, M., & Schambach, A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.143 · Cited by 76 · see citing works
Hinderer, S., Brauchle, E., & Schenke‐Layland, K. (2015) · Advanced Healthcare Materials · doi:10.1002/adhm.201400762 · Cited by 68 · see citing works
Roseman, D. S., Khan, T., Rajas, F., Jun, L. S., Asrani, K. H., Isaacs, C., Farelli, J. D., & Subramanian, R. R. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.01.006 · Cited by 72 · see citing works
Neutral Lipopolyplexes for In Vivo Delivery of Conventional and Replicative RNA Vaccine
Perche, F., Clemençon, R., Schulze, K., Ebensen, T., Guzmán, C. A., & Pichon, C. (2019) · Molecular Therapy - Nucleic Acids · doi:10.1016/j.omtn.2019.07.014 · Cited by 55 · see citing works
Lescan, M., Perl, R. M., Golombek, S., Pilz, M., Hann, L., Yasmin, M., Behring, A., Keller, T., Nolte, A., Gruhn, F., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.03.013 · Cited by 52 · see citing works
Gene Therapy for Inherited Retinal Degeneration
Arbabi, A., Liu, A., & Ameri, H. (2019) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2018.0087 · Cited by 30 · see citing works
mRNA treatment produces sustained expression of enzymatically active human ADAMTS13 in mice
Liu-Chen, S., Connolly, B., Cheng, L., Subramanian, R. R., & Han, Z. (2018) · Scientific Reports · doi:10.1038/s41598-018-26298-4 · Cited by 20 · see citing works
Tam, Y. K., Madden, T. D., & Hope, M. J. (2016) · Journal of Drug Targeting · doi:10.1080/1061186x.2016.1221955 · Cited by 20 · see citing works
Ai, X., Luo, R., Wang, H., Yan, B., Li, K., Yu, X., Dong, W., Tan, Y., Liu, M., Chen, Y., et al. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100776 · Cited by 14 · see citing works
- Authors
- Zangi, L., Lui, K. O., von Gise, A., Ma, Q., Ebina, W., Ptaszek, L. M., Später, D., Xu, H., Tabebordbar, M., Gorbatov, R., Sena, B., Nahrendorf, M., Briscoe, D. M., Li, R. A., Wagers, A. J., Rossi, D. J., Pu, W. T., & Chien, K. R.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Hong Kong (HK)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Pu, William T
- Chien, Kenneth R
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2013-09-08
- Volume
- 31
- Issue
- 10
- Pages
- 898-907
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC4058317
- OpenAlex
- W2098419906
- Cited by
- 646
- References
- 56
- Citations by year
- 2026: 31 · 2025: 47 · 2024: 46 · 2023: 49 · 2022: 55 · 2021: 60 · 2020: 51 · 2019: 50 · 2018: 61 · 2017: 45 · 2016: 56 · 2015: 49 · 2014: 36 · 2013: 9
- FWCI
- 22.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5u01hl100401-07, 1u01hl098166-01)
- U.S. Public Health Service (U01H100408, U01JL100401)
- National Heart, Lung, and Blood Institute (U01HL100402, RC1HL099618, U01-HL098166, R21HL104602, U01-HL-100401, R01HL094683)
- National Institute of Allergy and Infectious Diseases (R01AI092305)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- modified mRNA, VEGF-A, myocardial infarction, epicardial progenitor cells, paracrine signaling, vascular regeneration, intramyocardial injection, DNA vectors, VEGF inhibitors, cardiac function recovery
- MeSH terms
- Animals, Cell Differentiation, Disease Models, Animal, Humans, Kinetics, Luciferases, Models, Biological, Myocardial Infarction, Myocardium, Regeneration, RNA, Messenger, Stem Cells, Biomarkers, Survival Analysis, Treatment Outcome, Apoptosis, Gene Transfer Techniques, Muscle, Skeletal, Cell Lineage, Stem Cell Transplantation, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Endothelial Cells, Cell Proliferation, Mice
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
