Unlocking the promise of mRNA therapeutics
Open accessAbstract
The extraordinary success of mRNA vaccines against coronavirus disease 2019 (COVID-19) has renewed interest in mRNA as a means of delivering therapeutic proteins. Early clinical trials of mRNA therapeutics include studies of paracrine vascular endothelial growth factor (VEGF) mRNA for heart failure and of CRISPR-Cas9 mRNA for a congenital liver-specific storage disease. However, a series of challenges remains to be addressed before mRNA can be established as a general therapeutic modality with broad relevance to both rare and common diseases. An array of new technologies is being developed to surmount these challenges, including approaches to optimize mRNA cargos, lipid carriers with inherent tissue tropism and in vivo percutaneous delivery systems. The judicious integration of these advances may unlock the promise of biologically targeted mRNA therapeutics, beyond vaccines and other immunostimulatory agents, for the treatment of diverse clinical indications.
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?
Our results suggest their potential utility in both mRNA therapeutics and mRNA vaccines.
“Our results suggest their potential utility in both mRNA therapeutics and mRNA vaccines -the two key areas for the application of mRNA-based drugs [38].”
From Identification of novel 5’ UTR variants for enhanced mRNA translation and vaccine immunogenicity (2026) · cites this paper as [38]
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
Part of this paper’s reference list could not be split into single entries.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Polack, F. P., Thomas, S. J., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Perez, J. L., Pérez Marc, G., Moreira, E. D., Zerbini, C., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2034577 · Cited by 14,592 · cited 2× · see citing works
“Similarly to what occurs in the renal artery, increased localized pressure in the renal capillaries creates transient pores on cell membranes, resulting in nucleic acid extravasation(149); (3) retrograde ureteral, targeting the tubular epithelium; and (4) intraparenchymal, with a few reports demonstrating the suitabil…”
BackgroundThe biology <b>,</b> function <b>,</b> and biomedical applications of exosomes
Kalluri, R., & LeBleu, V. S. (2020) · Science · doi:10.1126/science.aau6977 · Cited by 10,770 · see citing works
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine
Baden, L. R., El Sahly, H. M., Essink, B., Kotloff, K., Frey, S., Novak, R., Diemert, D., Spector, S. A., Rouphael, N., Creech, C. B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2035389 · Cited by 10,119 · see citing works
Principles of nanoparticle design for overcoming biological barriers to drug delivery
Blanco, E., Shen, H., & Ferrari, M. (2015) · Nature Biotechnology · doi:10.1038/nbt.3330 · Cited by 7,002 · 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
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 · see citing works
Rational design of cationic lipids for siRNA delivery
Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822 · see citing works
CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis
Gillmore, J. D., Gane, E., Taubel, J., Kao, J., Fontana, M., Maitland, M. L., Seitzer, J., O’Connell, D., Walsh, K. R., Wood, K., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107454 · Cited by 1,766 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma
Sahin, U., Oehm, P., Derhovanessian, E., Jabulowsky, R. A., Vormehr, M., Gold, M., Maurus, D., Schwarck-Kokarakis, D., Kuhn, A. N., Omokoko, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2537-9 · Cited by 1,052 · see citing works
Engineering circular RNA for potent and stable translation in eukaryotic cells
Wesselhoeft, R. A., Kowalski, P. S., & Anderson, D. G. (2018) · Nature Communications · doi:10.1038/s41467-018-05096-6 · Cited by 884 · see citing works
Finn, J. D., Smith, A. R., Patel, M. C., Shaw, L., Youniss, M. R., van Heteren, J., Dirstine, T., Ciullo, C., Lescarbeau, R., Seitzer, J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.014 · Cited by 878 · see citing works
Codon optimality, bias and usage in translation and mRNA decay
Hanson, G., & Coller, J. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.91 · Cited by 825 · 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
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation
Anderson, B. R., Muramatsu, H., Nallagatla, S. R., Bevilacqua, P. C., Sansing, L. H., Weissman, D., & Karikó, K. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq347 · Cited by 682 · see citing works
Holtkamp, S., Kreiter, S., Selmi, A., Simon, P., Koslowski, M., Huber, C., Türeci, O., & Sahin, U. (2006) · Blood · doi:10.1182/blood-2006-04-015024 · Cited by 625 · see citing works
Anti‐ <scp>PEG</scp> immunity: emergence, characteristics, and unaddressed questions
Yang, Q., & Lai, S. K. (2015) · WIREs Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1339 · Cited by 593 · see citing works
Yim, N., Ryu, S.-W., Choi, K., Lee, K. R., Lee, S., Choi, H., Kim, J., Shaker, M. R., Sun, W., Park, J.-H., et al. (2016) · Nature Communications · doi:10.1038/ncomms12277 · Cited by 578 · see citing works
Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson’s disease
Qu, M., Lin, Q., Huang, L., Fu, Y., Wang, L., He, S., Fu, Y., Yang, S., Zhang, Z., Zhang, L., et al. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.08.035 · Cited by 543 · 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
RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo
Wesselhoeft, R. A., Kowalski, P. S., Parker-Hale, F. C., Huang, Y., Bisaria, N., & Anderson, D. G. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.02.015 · Cited by 482 · see citing works
Shimabukuro, T. T., Cole, M., & Su, J. R. (2021) · JAMA · doi:10.1001/jama.2021.1967 · Cited by 475 · see citing works
McKay, P. F., Hu, K., Blakney, A. K., Samnuan, K., Brown, J. C., Penn, R., Zhou, J., Bouton, C. R., Rogers, P., Polra, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17409-9 · Cited by 462 · see citing works
Feldman, R. A., Fuhr, R., Smolenov, I., (Mick) Ribeiro, A., Panther, L., Watson, M., Senn, J. J., Smith, M., Almarsson, Ӧ., Pujar, H. S., et al. (2019) · Vaccine · doi:10.1016/j.vaccine.2019.04.074 · Cited by 454 · see citing works
Human 5′ UTR design and variant effect prediction from a massively parallel translation assay
Sample, P. J., Wang, B., Reid, D. W., Presnyak, V., McFadyen, I. J., Morris, D. R., & Seelig, G. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0164-5 · Cited by 442 · see citing works
Maintaining safety with SARS-CoV-2 vaccines
Castells, M. C., & Phillips, E. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2035343 · Cited by 395 · see citing works
Impact of mRNA chemistry and manufacturing process on innate immune activation
Nelson, J., Sorensen, E. W., Mintri, S., Rabideau, A. E., Zheng, W., Besin, G., Khatwani, N., Su, S. V., Miracco, E. J., Issa, W. J., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz6893 · Cited by 354 · see citing works
Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia
An, D., Schneller, J. L., Frassetto, A., Liang, S., Zhu, X., Park, J.-S., Theisen, M., Hong, S.-J., Zhou, J., Rajendran, R., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.081 · Cited by 263 · see citing works
Vaidyanathan, S., Azizian, K. T., Haque, A. K. M. A., Henderson, J. M., Hendel, A., Shore, S., Antony, J. S., Hogrefe, R. I., Kormann, M. S. D., Porteus, M. H., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.06.010 · Cited by 262 · see citing works
Tardieu, M., Zérah, M., Husson, B., de Bournonville, S., Deiva, K., Adamsbaum, C., Vincent, F., Hocquemiller, M., Broissand, C., Furlan, V., et al. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.238 · Cited by 261 · see citing works
Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery
Nogueira, S. S., Schlegel, A., Maxeiner, K., Weber, B., Barz, M., Schroer, M. A., Blanchet, C. E., Svergun, D. I., Ramishetti, S., Peer, D., et al. (2020) · ACS Applied Nano Materials · doi:10.1021/acsanm.0c01834 · Cited by 252 · see citing works
Henderson, J. M., Ujita, A., Hill, E., Yousif‐Rosales, S., Smith, C., Ko, N., McReynolds, T., Cabral, C. R., Escamilla‐Powers, J. R., & Houston, M. E. (2021) · Current Protocols · doi:10.1002/cpz1.39 · Cited by 231 · see citing works
Zhu, X., Yin, L., Theisen, M., Zhuo, J., Siddiqui, S., Levy, B., Presnyak, V., Frassetto, A., Milton, J., Salerno, T., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.02.003 · Cited by 165 · see citing works
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2022) · Nature · doi:10.1038/s41586-021-04231-6 · Cited by 127 · see citing works
Amplifying RNA Vaccine Development
Fuller, D. H., & Berglund, P. (2020) · New England Journal of Medicine · doi:10.1056/nejmcibr2009737 · Cited by 116 · see citing works
Systemic modified messenger RNA for replacement therapy in alpha 1-antitrypsin deficiency
Karadagi, A., Cavedon, A. G., Zemack, H., Nowak, G., Eybye, M. E., Zhu, X., Guadagnin, E., White, R. A., Rice, L. M., Frassetto, A. L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-64017-0 · Cited by 54 · see citing works
Flagged first, then by citations
Research works printed but not linked: 24
- Vlatkovic, I. Non-immunotherapy application of LNP-mRNA: maximizing efficacy and safety. Biomedicines 9, 530 (2021).
- Shi, D. et al. To PEGylate or not to PEGylate: immunological properties of nanomedicine's most popular component, polyethylene glycol and its alternatives. Adv. Drug Deliv. Rev. 180, 114079 (2022).
- Connolly, B., Isaacs, C., Cheng, L., Asrani, K. H. & Subramanian, R. R. SERPINA1 mRNA as a treatment for alpha-1 antitrypsin deficiency. J. Nucleic Acids 2018, 8247935 (2018).
- Ramaswamy, S. et al. Systemic delivery of factor IX messenger RNA for protein replacement therapy. Proc. Natl Acad. Sci. USA 114, E1941-E1950 (2017).
- Jiang, L. et al. Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia. Nat. Commun. 11, 5339 (2020).
- Haque, A. K. M. A. et al. Chemically modified hCFTR mRNAs recuperate lung function in a mouse model of cystic fibrosis. Sci. Rep. 8, 16776 (2018).
- De Genst, E. et al. Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure. Nat. Commun. 13, 3018 (2022).
- Cao, J. et al. mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease. Nat. Commun. 12, 3090 (2021).
- Patel, M. et al. 539 Phase 1 study of mRNA-2752, a lipid nanoparticle encapsulating mRNAs encoding human OX40L/ IL-23/IL-36γ, for intratumoral (ITu) injection +/-durvalumab in advanced solid tumors and lymphoma. J. Immunother. Cancer https://doi.org/10.1136/jitc-2021-SITC2021.539 (2021). · DOI
- Grier, A. E. et al. pEVL: a linear plasmid for generating mRNA IVT templates with extended encoded poly(A) sequences. Mol. Ther. Nucleic Acids 5, e306 (2016).
- Martin, C. & Lowery, D. mRNA vaccines: intellectual property landscape. Nat. Rev. Drug Discov. 19, 578-578 (2020). Review Article https://doi.org/10.1038/s41587-022-01491-z
- Schaefer, M., Kapoor, U. & Jantsch, M. F. Understanding RNA modifications: the promises and technological bottlenecks of the 'epitranscriptome'. Open Biol. 7, 170077 (2017).
- Fu, H. et al. Codon optimization with deep learning to enhance protein expression. Sci. Rep. 10, 17617 (2020).
- Kim, D. Y. et al. Enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic RNAs. Proc. Natl Acad. Sci. USA 111, 10708-10713 (2014).
- Kariko, K. & Muramatsu, H. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 39, 10 (2011).
- Malone, R. W., Felgner, P. L. & Verma, I. M. Cationic liposome- mediated RNA transfection. Proc. Natl Acad. Sci. USA 86, 6077-6081 (1989).
- Sercombe, L. et al. Advances and challenges of liposome assisted drug delivery. Front. Pharmacol. 6, 286 (2015).
- Han, X. et al. An ionizable lipid toolbox for RNA delivery. Nat. Commun. 12, 7233 (2021).
- Jayaraman, M. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int. Ed. Engl. 51, 8529-8533 (2012). Review Article https://doi.org/10.1038/s41587-022-01491-z
- Pasut, G. & Zalipsky, S. (eds). Polymer-Protein Conjugates 1st edn (Elsevier, 2019).
- Kroll, A. V. et al. Nanoparticulate delivery of cancer cell membrane elicits multiantigenic antitumor immunity. Adv. Mater. 29, 10.1002/adma.201703969 (2017). 136. Zhang, W. et al. Tumor microenvironment-activated cancer cell membrane-liposome hybrid nanoparticle-mediated synergistic metabolic therapy and chemotherapy for non-small cell lung cancer. J. Nanobiotechnology 19, 339 (2021). 137. Zhang, R. et al. Particle-based artificial three-dimensional stem cell spheroids for revascularization of ischemic diseases. Sci. Adv. 6, eaaz8011 (2020). 138. Dehaini, D. et al. Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization. Adv. Mater. 29, 1606209 (2017). 139. Wang, D. et al. Erythrocyte-cancer hybrid membrane camouflaged hollow copper sulfide nanoparticles for prolonged circulation life and homotypic-targeting photothermal/ chemotherapy of melanoma. ACS Nano 12, 5241-5252 (2018). 140. Gong, C. et al. Macrophage-cancer hybrid membrane-coated nanoparticles for targeting lung metastasis in breast cancer therapy. J. Nanobiotechnology 18, 92 (2020). 141. Rao, L. et al. Platelet-leukocyte hybrid membrane-coated immunomagnetic beads for highly efficient and highly specific isolation of circulating tumor cells. Adv. Funct. Mater. 28, 1803531 (2018). 142. Sato, Y. T. et al. Engineering hybrid exosomes by membrane fusion with liposomes. Sci. Rep. 6, 21933 (2016). 143. Li, Y.-J. et al. Artificial exosomes for translational nanomedicine. J. Nanobiotechnology 19, 242 (2021). 144. Lathwal, S. et al. Engineering exosome polymer hybrids by atom transfer radical polymerization. Proc. Natl Acad. Sci. USA 118, e2020241118 (2021). 145. Lv, Q. et al. Thermosensitive exosome-liposome hybrid nanoparticle-mediated chemoimmunotherapy for improved treatment of metastatic peritoneal cancer. Adv. Sci. 7, 2000515 (2020). 146. Grankvist, R. et al. Superselective endovascular tissue access using trans-vessel wall technique: feasibility study for treatment applications in heart, pancreas and kidney in swine. J. Intern. Med. 285, 398-406 (2019). 147. Rubin, J. D. & Barry, M. A. Improving molecular therapy in the kidney. Mol. Diagn. Ther. 24, 375-396 (2020). 148. Gao, S. et al. Megalin-mediated specific uptake of chitosan/ siRNA nanoparticles in mouse kidney proximal tubule epithelial cells enables AQP1 gene silencing. Theranostics 4, 1039-1051 (2014). 149. Zheng, X. et al. Attenuating ischemia-reperfusion injury in kidney transplantation by perfusing donor organs with siRNA cocktail solution. Transplantation 100, 743-752 (2016). 150. Davis, L. & Park, F. Gene therapy research for kidney diseases. Physiol. Genomics 51, 449-461 (2019). 151. Espana-Agusti, J., Tuveson, D. A., Adams, D. J. & Matakidou, A. A minimally invasive, lentiviral based method for the rapid and sustained genetic manipulation of renal tubules. Sci. Rep. 5, 11061 (2015). 152. Merkel, O. M., Rubinstein, I. & Kissel, T. siRNA delivery to the lung: what's new? Adv. Drug Deliv. Rev. 75, 112-128 (2014). 153. Arulmuthu, E. R., Williams, D. J., Baldascini, H., Versteeg, H. K. & Hoare, M. Studies on aerosol delivery of plasmid DNA using a mesh nebulizer. Biotechnol. Bioeng. 98, 939-955 (2007). 154. Translate Bio, Inc. A phase 1/2, randomized, double-blinded, placebo-controlled, combined single and multiple ascending dose study evaluating the safety, tolerability, and biological activity of MRT5005 administered by nebulization to adult subjects with cystic fibrosis (RESTORE-CF). https://clinicaltrials. gov/ct2/show/NCT03375047 155. · DOI
- Daneman, R. & Prat, A. The blood-brain barrier. Cold Spring Harb. Perspect. Biol. 7, a020412 (2015). 158. Piguet, F. et al. The challenge of gene therapy for neurological diseases: strategies and tools to achieve efficient delivery to the central nervous system. Hum. Gene Ther. 32, 349-374 (2021). 159.
- Cannatà, A., Ali, H., Sinagra, G. & Giacca, M. Gene therapy for the heart lessons learned and future perspectives. Circ. Res. 126, 1394-1414 (2020). 172. Li, J. et al. All roads lead to Rome (the heart): cell retention and outcomes from various delivery routes of cell therapy products to the heart. J. Am. Heart Assoc. 10, e020402 (2021). 173. Lundberg, J., Grankvist, R. & Holmin, S. The creation of an endovascular exit through the vessel wall using a minimally invasive working channel in order to reach all human organs. J. Intern. Med. 286, 309-316 (2019). 174. Katz, M. G., Fargnoli, A. S., Kendle, A. P. & Bridges, C. R. Molecular Cardiac Surgery with Recirculating Delivery (MCARD): procedure and vector transfer. in Cardiac Gene Therapy: Methods and Protocols (ed Ishikawa, K.) 271-289 (Springer, 2017). Review Article https://doi.org/10.1038/s41587-022-01491-z 175. · DOI
- Collén, A. et al. VEGF-A mRNA for regenerative treatment of heart failure. Nat. Rev. Drug Discov. 21, 79-80 (2022). 216. Chien, K. R., Zangi, L. & Lui, K. O. Synthetic chemically modified mRNA (modRNA): toward a new technology platform for cardiovascular biology and medicine. Cold Spring Harb. Perspect. Med. 5, a014035 (2014). 217. Intellia and Regeneron announce updated phase 1 data demonstrating a single dose of NTLA-2001, an investigational CRISPR therapy for transthyretin (ATTR) amyloidosis, resulted in rapid, deep and sustained reduction in disease-causing protein. https://ir.intelliatx.com/news-releases/news-release-details/ intellia-and-regeneron-announce-updated-phase-1-data (2022). 218. Yu, F. et al. Human adipose-derived stem cells enriched with VEGF-modified mRNA promote angiogenesis and long-term graft survival in a fat graft transplantation model. Stem Cell Res. Ther. 11, 490 (2020). 219. Rohner, E. et al. An mRNA assay system demonstrates proteasomal-specific degradation contributes to cardio- myopathic phospholamban null mutation. Mol. Med. 27, 102 (2021). 220. Omer-Javed, A. et al. Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells. Cell 185, 2248-2264 (2022).
Cited by
Sorted by citations
mRNA-based cancer therapeutics
Liu, C., Shi, Q., Huang, X., Koo, S., Kong, N., & Tao, W. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-023-00586-2 · Cited by 500 · see citing works
Exosome for mRNA delivery: Strategies and therapeutic applications
Iqbal, Z., Rehman, K., Mahmood, A., Shabbir, M., Liang, Y., Duan, L., & Zeng, H. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02634-x · Cited by 144 · see citing works
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
- Rohner, E., Yang, R., Foo, K. S., Goedel, A., & Chien, K. R.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Nature Biotechnology
- Published
- 2022-11
- Volume
- 40
- Issue
- 11
- Pages
- 1586-1600
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W4308101956
- Cited by
- 612
- References
- 37
- Citations by year
- 2026: 173 · 2025: 202 · 2024: 159 · 2023: 75 · 2022: 3
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse (KAW 2013.0028)
- Vetenskapsrådet
- H2020 European Research Council (743225)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- mRNA therapeutics, mRNA vaccines, COVID-19 pandemic, heart failure, lipid carriers, tissue tropism, rare diseases
- MeSH terms
- COVID-19, COVID-19 Vaccines, Genetic Vectors, Humans, RNA, Messenger, Vascular Endothelial Growth Factor A
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
