1 of 3,802

Towards mRNA therapeutics 2.0 – Nature Reviews Drug Discovery


  • Kallen, K.-J. et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive® vaccines. Hum. Vaccin. Immunother. 9, 2263–2276 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hogan, M. J. & Pardi, N. mRNA vaccines in the COVID-19 pandemic and beyond. Annu. Rev. Med. 73, 17–39 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aliprantis, A. O. et al. A phase 1, randomized, placebo-controlled study to evaluate the safety and immunogenicity of an mRNA-based RSV prefusion F protein vaccine in healthy younger and older adults. Hum. Vacc. Immunother. 17, 1248–1261 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Wilson, E. et al. Efficacy and safety of an mRNA-based RSV PreF vaccine in older adults. N. Engl. J. Med. 389, 2233–2244 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shaw, C. A. et al. Safety and immunogenicity of an mRNA-based RSV vaccine including a 12-month booster in a phase 1 clinical trial in healthy older adults. J. Infect. Dis. 230, e647–e656 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arevalo, C. P. et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 378, 899–904 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, I. T. et al. Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. Nat. Commun. 14, 3631 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hu, X. et al. Human cytomegalovirus mRNA-1647 vaccine candidate elicits potent and broad neutralization and higher antibody-dependent cellular cytotoxicity responses than the gB/MF59 vaccine. J. Infect. Dis. 230, 455–466 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, K. et al. Characterization of humoral and cellular immunologic responses to an mRNA-based human cytomegalovirus vaccine from a phase 1 trial of healthy adults. J. Virol. 98, e01603-23 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fierro, C. et al. Safety and immunogenicity of a messenger RNA-based cytomegalovirus vaccine in healthy adults: results from a phase 1 randomized clinical trial. J. Infect. Dis. 230, e668–e678 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Parhiz, H., Atochina-Vasserman, E. N. & Weissman, D. mRNA-based therapeutics: looking beyond COVID-19 vaccines. Lancet 403, 1192–1204 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rohner, E., Yang, R., Foo, K. S., Goedel, A. & Chien, K. R. Unlocking the promise of mRNA therapeutics. Nat. Biotechnol. 40, 1586–1600 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Metkar, M., Pepin, C. S. & Moore, M. J. Tailor made: the art of therapeutic mRNA design. Nat. Rev. Drug. Discov. 23, 67–83 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tsuchida, C. A., Wasko, K. M., Hamilton, J. R. & Doudna, J. A. Targeted nonviral delivery of genome editors in vivo. Proc. Natl Acad. Sci. USA 121, e2307796121 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mendonça, M. C. P., Kont, A., Kowalski, P. S. & O’Driscoll, C. M. Design of lipid-based nanoparticles for delivery of therapeutic nucleic acids. Drug Discov. Today 28, 103505 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Yuan, Y. et al. Intelligent design of lipid nanoparticles for enhanced gene therapeutics. Mol. Pharm. https://doi.org/10.1021/acs.molpharmaceut.4c00925 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dolgin, E. The tangled history of mRNA vaccines. Nature 597, 318–324 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shi, Y., Shi, M., Wang, Y. & You, J. Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications. Sig Transduct. Target. Ther. 9, 1–43 (2024).

    Article 

    Google Scholar
     

  • Fuller, D. H. & Berglund, P. Amplifying RNA vaccine development. N. Engl. J. Med. 382, 2469–2471 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines—a new era in vaccinology. Nat. Rev. Drug. Discov. 17, 261–279 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gote, V. et al. A comprehensive review of mRNA vaccines. Int. J. Mol. Sci. 24, 2700 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, S. et al. Nanotechnology-based mRNA vaccines. Nat. Rev. Methods Primers 3, 1–19 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).

    Article 
    PubMed 

    Google Scholar
     

  • Gómez-Aguado, I. et al. mRNA delivery technologies: toward clinical translation. Int. Rev. Cell Mol. Biol. 372, 207–293 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Ige, M. A. et al. mRNA therapeutics: transforming medicine through innovation in design, delivery, and disease treatment. Mol. Ther. Nucleic Acids 36, 102721 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sonenberg, N. & Gingras, A.-C. The mRNA 5′ cap-binding protein eIF4E and control of cell growth. Curr. Opin. Cell Biol. 10, 268–275 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Grudzien, E. et al. Novel cap analogs for in vitro synthesis of mRNAs with high translational efficiency. RNA 10, 1479–1487 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Y. & Kiledjian, M. Regulation of mRNA decapping. WIREs RNA 1, 253–265 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ziemniak, M., Strenkowska, M., Kowalska, J. & Jemielity, J. Potential therapeutic applications of RNA cap analogs. Future Med. Chem. 5, 1141–1172 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mandell, Z. F. et al. CleanCap M6 inhibits decapping of exogenously delivered IVT mRNA. Mol. Ther. Nucleic Acids 36, 102456 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Inagaki, M. et al. Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures. Nat. Commun. 14, 2657 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stepinski, J., Waddell, C., Stolarski, R., Darzynkiewicz, E. & Rhoads, R. E. Synthesis and properties of mRNAs containing the novel ‘anti-reverse’ cap analogs 7-methyl(3′-O-methyl)GpppG and 7-methyl (3′-deoxy)GpppG. RNA 7, 1486–1495 (2001).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Henderson, J. M. et al. Cap 1 Messenger RNA synthesis with co-transcriptional CleanCap® analog by in vitro transcription. Curr. Protoc. 1, e39 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mockey, M. et al. mRNA transfection of dendritic cells: synergistic effect of ARCA mRNA capping with poly(A) chains in cis and in trans for a high protein expression level. Biochem. Biophys. Res. Commun. 340, 1062–1068 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Casmil, I. C. et al. The advent of clinical self-amplifying RNA vaccines. Mol. Ther. 33, 2565–2582 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jia, L. et al. Decoding mRNA translatability and stability from the 5′ UTR. Nat. Struct. Mol. Biol. 27, 814–821 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sample, P. J. et al. Human 5′ UTR design and variant effect prediction from a massively parallel translation assay. Nat. Biotechnol. 37, 803–809 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barazandeh, S., Ozden, F., Hincer, A., Seker, U. O. S. & Cicek, A. E. UTRGAN: learning to generate 5′ UTR sequences for optimized translation efficiency and gene expression. Bioinforma. Adv. 5, vbaf134 (2024).

    Article 

    Google Scholar
     

  • Yang, Y. et al. Deciphering 3′UTR mediated gene regulation using interpretable deep representation learning. Adv. Sci. 11, e2407013 (2024).

    Article 

    Google Scholar
     

  • Morrow, A. K. et al. ML-driven design of 3′ UTRs for mRNA stability. Preprint at bioRxiv https://doi.org/10.1101/2024.10.07.616676 (2024).

  • Orlandini Von Niessen, A. G. et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3′ UTRs identified by cellular library screening. Mol. Ther. 27, 824–836 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ma, X. et al. Enhancing mRNA translation efficiency by introducing sequence optimized AU-rich elements in 3′ UTR via HuR anchorage. Mol. Ther. Nucleic Acids 36, 102485 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sultana, N. et al. Optimization of 5′ untranslated region of modified mRNA for use in cardiac or hepatic ischemic injury. Mol. Ther. Methods Clin. Dev. 17, 622–633 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, Y. et al. Deep generative optimization of mRNA codon sequences for enhanced mRNA translation and therapeutic efficacy. Nat. Commun. 16, 9957 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, H. et al. Algorithm for optimized mRNA design improves stability and immunogenicity. Nature 621, 396–403 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leppek, K. et al. Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics. Nat. Commun. 13, 1536 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hanson, G. & Coller, J. Codon optimality, bias and usage in translation and mRNA decay. Nat. Rev. Mol. Cell Biol. 19, 20–30 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Narula, A., Ellis, J., Taliaferro, J. M. & Rissland, O. S. Coding regions affect mRNA stability in human cells. RNA 25, 1751–1764 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karikó, K. Modified uridines are the key to a successful message. Nat. Rev. Immunol. 21, 619–619 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Karikó, K. et al. Incorporation of pseudouridine Into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nance, K. D. & Meier, J. L. Modifications in an emergency: the role of N1-methylpseudouridine in COVID-19 vaccines. ACS Cent. Sci. 7, 748–756 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schrum, J. P., Siddiqi, S. & Ejebe, K. Ribonucleic acids containing N1-methyl-pseudouracils and uses thereof. European Patent EP2622064B1 (18 May 2022).

  • Li, S. et al. CodonBERT large language model for mRNA vaccines. Genome Res. 34, 1027–1035 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • De Almeida, B. P. et al. A multimodal conversational agent for DNA, RNA and protein tasks. Nat. Mach. Intell. 7, 928–941 (2025).

    Article 

    Google Scholar
     

  • Thess, A. et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. 23, 1456–1464 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Biziaev, N. et al. The impact of mRNA poly(A) tail length on eukaryotic translation stages. Nucleic Acids Res. 52, 7792–7808 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stowell, J. A. W. et al. Reconstitution of targeted deadenylation by the Ccr4-Not complex and the YTH domain protein Mmi1. Cell Rep. 17, 1978–1989 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Passmore, L. A. & Coller, J. Roles of mRNA poly(A) tails in regulation of eukaryotic gene expression. Nat. Rev. Mol. Cell Biol. 23, 93–106 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiang, K. & Bartel, D. P. The molecular basis of coupling between poly(A)-tail length and translational efficiency. eLife 10, e66493 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, H. et al. Branched chemically modified poly(A) tails enhance the translation capacity of mRNA. Nat. Biotechnol. 43, 194–203 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aditham, A. et al. Chemically modified mocRNAs for highly efficient protein expression in mammalian cells. ACS Chem. Biol. 17, 3352–3366 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, C. Y. et al. Cytidine-containing tails robustly enhance and prolong protein production of synthetic mRNA in cell and in vivo. Mol. Ther. Nucleic Acids 30, 300–310 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, B. & Pan, T. Building better mRNA for therapeutics. Nat. Biotechnol. 43, 1058–1060 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cullis, P. R. & Hope, M. J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 25, 1467–1475 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 6, 1078–1094 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schoenmaker, L. et al. mRNA–lipid nanoparticle COVID-19 vaccines: structure and stability. Int. J. Pharm. 601, 120586 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schlake, T., Thess, A., Fotin-Mleczek, M. & Kallen, K.-J. Developing mRNA-vaccine technologies. RNA Biol. 9, 1319–1330 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hou, X., Shi, J. & Xiao, Y. mRNA medicine: recent progresses in chemical modification, design, and engineering. Nano Res. 17, 9015–9030 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dilliard, S. A. & Siegwart, D. J. Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs. Nat. Rev. Mater. 8, 282–300 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dowdy, S. F. Overcoming cellular barriers for RNA therapeutics. Nat. Biotechnol. 35, 222–229 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mosser, D. M. & Edwards, J. P. Exploring the full spectrum of macrophage activation. Nat. Rev. Immunol. 8, 958–969 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nie, Q. et al. Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation. Acta Pharm. Sin. B 13, 390–409 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Romero, E. L., Morilla, M.-J., Regts, J., Koning, G. A. & Scherphof, G. L. On the mechanism of hepatic transendothelial passage of large liposomes. FEBS Lett. 448, 193–196 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, M. et al. Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver. Sci. Adv. 7, eabf4398 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cullis, P. R. & Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug. Discov. 23, 709–722 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, Y., Jeong, M., Park, J., Jung, H. & Lee, H. Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics. Exp. Mol. Med. 55, 2085–2096 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaudhary, N. et al. Amine headgroups in ionizable lipids drive immune responses to lipid nanoparticles by binding to the receptors TLR4 and CD1d. Nat. Biomed. Eng. 8, 1483–1498 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lui, K. O. et al. Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA. Cell Res. 23, 1172–1186 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xie, C., Yao, R. & Xia, X. The advances of adjuvants in mRNA vaccines. npj Vaccines 8, 162 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Warne, N. et al. Delivering 3 billion doses of Comirnaty in 2021. Nat. Biotechnol. https://doi.org/10.1038/s41587-022-01643-1 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Almquist, J. et al. Model-based analysis reveals a sustained and dose-dependent acceleration of wound healing by VEGF-A mRNA (AZD8601). CPT Pharmacom Syst. Pharma 9, 384–394 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Carlsson, L. et al. Biocompatible, purified VEGF-A mRNA improves cardiac function after intracardiac injection 1 week post-myocardial infarction in swine. Mol. Ther. Methods Clin. Dev. 9, 330–346 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lui, K. O., Zangi, L. & Chien, K. R. Cardiovascular regenerative therapeutics via synthetic paracrine factor modified mRNA. Stem Cell Res. 13, 693–704 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun, N. et al. Modified VEGF-A mRNA induces sustained multifaceted microvascular response and accelerates diabetic wound healing. Sci. Rep. 8, 17509 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zangi, L. et al. Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction. Nat. Biotechnol. 31, 898–907 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gan, L.-M. et al. Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes. Nat. Commun. 10, 871 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Collén, A. et al. VEGFA mRNA for regenerative treatment of heart failure. Nat. Rev. Drug Discov. 21, 79–80 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anttila, V. et al. Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting. Mol. Ther. 31, 866–874 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yu, Z. et al. Cell-mediated delivery of VEGF modified mRNA enhances blood vessel regeneration and ameliorates murine critical limb ischemia. J. Control. Rel. 310, 103–114 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Ai, X. et al. Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI. Mol. Ther. 31, 211–229 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Engel, J. E., Williams, E., Williams, M. L., Bidwell, G. L. & Chade, A. R. Targeted VEGF (vascular endothelial growth factor) therapy induces long-term renal recovery in chronic kidney disease via macrophage polarization. Hypertension 74, 1113–1123 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Geng, Y. et al. BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways. Commun. Biol. 4, 82 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • 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).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liric Rajlic, I. et al. Translational kinetic-pharmacodynamics of mRNA-6231, an investigational mRNA therapeutic encoding mutein interleukin-2. CPT Pharmacom Syst. Pharma 13, 1067–1078 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Lykhopiy, V., Malviya, V., Humblet-Baron, S. & Schlenner, S. M. IL-2 immunotherapy for targeting regulatory T cells in autoimmunity. Genes. Immun. 24, 248–262 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Raeber, M. E., Sahin, D., Karakus, U. & Boyman, O. A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases. eBioMedicine 90, 104539 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mikami, N., Kawakami, R. & Sakaguchi, S. New Treg cell-based therapies of autoimmune diseases: towards antigen-specific immune suppression. Curr. Opin. Immunol. 67, 36–41 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Konrad, M. W. et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Res. 50, 2009–2017 (1990).

    CAS 
    PubMed 

    Google Scholar
     

  • Wardell, C. M., Boardman, D. A. & Levings, M. K. Harnessing the biology of regulatory T cells to treat disease. Nat. Rev. Drug. Discov. 24, 93–111 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • De Picciotto, S. et al. Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein. Nat. Commun. 13, 3866 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zeng, J. et al. Antitumor activity of Z15-0-2, a bispecific nanobody targeting PD-1 and CTLA-4. Oncogene 43, 2244–2252 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chung, E. et al. Abstract 1368: Novel mRNA encoding anti-PD-L1 monoclonal antibodies for cancer immunotherapy. Cancer Res. 84, 1368 (2024).

    Article 

    Google Scholar
     

  • Pardi, N. et al. Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge. Nat. Commun. 8, 14630 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stadler, C. R. et al. Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. Nat. Med. 23, 815–817 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • De Vlieger, D. et al. Selective engagement of FcγRIV by a M2e-specific single domain antibody construct protects against influenza A virus infection. Front. Immunol. 10, 2920 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van Hoecke, L. et al. mRNA encoding a bispecific single domain antibody construct protects against influenza A virus infection in mice. Mol. Ther. Nucleic Acids 20, 777–787 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yap, T. A. et al. First-in-human phase I/II trial evaluating BNT142, a first-in-class mRNA encoded, bispecific antibody targeting Claudin 6 (CLDN6) and CD3, in patients (pts) with CLDN6-positive advanced solid tumors. J. Clin. Oncol. 43, 2501 (2025).

    Article 

    Google Scholar
     

  • Aboul-Ella, H. et al. Monoclonal antibodies: from magic bullet to precision weapon. Mol. Biomed. 5, 47 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, Y., Gan, L., Ke, D., Chen, Q. & Fu, Y. Mechanisms and research advances in mRNA antibody drug-mediated passive immunotherapy. J. Transl. Med. 21, 693 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Van Hoecke, L. & Roose, K. How mRNA therapeutics are entering the monoclonal antibody field. J. Transl. Med. 17, 54 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • August, A. et al. A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus. Nat. Med. 27, 2224–2233 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hennigan, J. N. & Lynch, M. D. The past, present, and future of enzyme-based therapies. Drug. Discov. Today 27, 117–133 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vavilis, T. et al. mRNA in the context of protein replacement therapy. Pharmaceutics 15, 166 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Byrne, B. J. et al. Current clinical applications of AAV-mediated gene therapy. Mol. Ther. 33, 2479–2516 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brunetti-Pierri, N. & Lee, B. Gene therapy for inborn errors of liver metabolism. Mol. Genet. Metab. 86, 13–24 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wolff, J. A. et al. Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468 (1990).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jirikowski, G. F., Sanna, P. P., Maciejewski-Lenoir, D. & Bloom, F. E. Reversal of diabetes insipidus in Brattleboro rats: intrahypothalamic injection of vasopressin mRNA. Science 255, 996–998 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Koeberl, D. et al. Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia. Nature 628, 872–877 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chandler, R. J. et al. Mitochondrial dysfunction in mut methylmalonic acidemia. FASEB J. 23, 1252–1261 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Head, P. E., Meier, J. L. & Venditti, C. P. New insights into the pathophysiology of methylmalonic acidemia. J. Inher Metab. Disea 46, 436–449 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Fenton, W. A., Gravel, R. A. & Rosenblatt, D. S. Disorders of propionate and methylmalonate metabolism. In The Online Metabolic and Molecular Bases of Inherited Disease (eds Valle, D. L. et al.) Ch. 94 (McGraw-Hill Education, 2019).

  • Svitkin, Y. V. et al. N1-Methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res. 45, 6023–6036 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Desmet, C. J. & Ishii, K. J. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat. Rev. Immunol. 12, 479–491 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Coughlan, K. A. et al. Improved therapeutic efficacy in two mouse models of methylmalonic acidemia (MMA) using a second-generation mRNA therapy. Mol. Genet. Metab. 143, 108560 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Marion, R. W. & Paljevic, E. The glycogen storage disorders. Pediatr. Rev. 41, 41–44 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Derks, T. G. J. et al. Glycogen storage disease type Ia: current management options, burden and unmet needs. Nutrients 13, 3828 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wright, T. L. F., Umaña, L. A. & Ramirez, C. M. Update on glycogen storage disease: primary hepatic involvement. Curr. Opin. Pediatr. 34, 496–502 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Kishnani, P. S., Sun, B. & Koeberl, D. D. Gene therapy for glycogen storage diseases. Hum. Mol. Genet. 28, R31–R41 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mitchell, J. et al. Efficacy and safety results from a pivotal phase 3 trial of DTX401, an AAV8-mediated liver-directed gene therapy, in individuals with glycogen storage disease type Ia (GSDIa). Endocrine Abstracts https://doi.org/10.1530/endoabs.110.RC3.6 (2025).

    Article 

    Google Scholar
     

  • Weinstein, D. A. et al. Safety and efficacy of DTX401, an AAV8-mediated liver-directed gene therapy, in adults with glycogen storage disease type I a (GSDIa). J. Inher. Metab. Dis. 48, e70014 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roseman, D. S. et al. G6PC mRNA therapy positively regulates fasting blood glucose and decreases liver abnormalities in a mouse model of glycogen storage disease 1a. Mol. Ther. 26, 814–821 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, J. et al. mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease. Nat. Commun. 12, 3090 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cunningham, S. C., Dane, A. P., Spinoulas, A. & Alexander, I. E. Gene delivery to the juvenile mouse liver using AAV2/8 vectors. Mol. Ther. 16, 1081–1088 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yiu, W. H. et al. Complete normalization of hepatic G6PC deficiency in murine glycogen storage disease type Ia using gene therapy. Mol. Ther. 18, 1076–1084 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weber, T. Anti-AAV antibodies in AAV gene therapy: current challenges and possible solutions. Front. Immunol. 12, 658399 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arnaoutova, I. et al. Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia. Nat. Commun. 15, 9729 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Okechuku, G. O. et al. Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy. J. Inher. Metab. Dis. 40, 703–708 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beegle, R. D., Brown, L. M. & Weinstein, D. A. Regression of hepatocellular adenomas with strict dietary therapy in patients with glycogen storage disease type I. In JIMD Reports, Vol. 18 (eds Zschocke, J. et al.) (Springer, 2014).

  • Dambska, M., Labrador, E., Kuo, C. & Weinstein, D. Prevention of complications in glycogen storage disease type Ia with optimization of metabolic control: Dambska et al. Pediatr. Diabetes 18, 327–331 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gómez-Aguado, I. et al. Nanomedicines to deliver mRNA: state of the art and future perspectives. Nanomaterials 10, 364 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04416126 (2023).

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06488313 (2025).

  • Weng, Y. et al. The challenge and prospect of mRNA therapeutics landscape. Biotechnol. Adv. 40, 107534 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Y.-N., Poon, W., Tavares, A. J., McGilvray, I. D. & Chan, W. C. W. Nanoparticle–liver interactions: cellular uptake and hepatobiliary elimination. J. Control. Rel. 240, 332–348 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Lam, K. et al. Optimizing lipid nanoparticles for delivery in primates. Adv. Mater. 35, e2211420 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Han, X. et al. Optimization of the activity and biodegradability of ionizable lipids for mRNA delivery via directed chemical evolution. Nat. Biomed. Eng. 8, 1412–1424 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, W. et al. Artificial intelligence-driven rational design of ionizable lipids for mRNA delivery. Nat. Commun. 15, 10804 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Han, X. et al. An ionizable lipid toolbox for RNA delivery. Nat. Commun. 12, 7233 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Böttger, R. et al. Lipid-based nanoparticle technologies for liver targeting. Adv. Drug. Delivery Rev. 154–155, 79–101 (2020).

    Article 

    Google Scholar
     

  • Daly, O. et al. ASL mRNA–LNP therapeutic for the treatment of argininosuccinic aciduria enables survival benefit in a mouse model. Biomedicines 11, 1735 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weide, B. et al. Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J. Immunother. 32, 498 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sahin, U., Karikó, K. & Türeci, Ö mRNA-based therapeutics—developing a new class of drugs. Nat. Rev. Drug. Discov. 13, 759–780 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mullard, A. COVID-19 vaccine success enables a bolder vision for mRNA cancer vaccines, says BioNTech CEO. Nat. Rev. Drug. Discov. 20, 500–501 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cafri, G. et al. Immunogenicity and tolerability of personalized mRNA vaccine mRNA-4650 encoding defined neoantigens expressed by the autologous cancer. J. Clin. Oncol. 37, 2643–2643 (2019).

    Article 

    Google Scholar
     

  • Dolgin, E. How personalized cancer vaccines could keep tumours from coming back. Nature 630, 290–292 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sahin, U. et al. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547, 222–226 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Weber, J. S. et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet 403, 632–644 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, D. S. & Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature 541, 321–330 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Palmer, C. D. et al. Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results. Nat. Med. 28, 1619–1629 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yadav, M. et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515, 572–576 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yang, S., Ta, Y.-N. N. & Chen, Y. Nanotechnology-enhanced immunotherapies for pancreatic ductal adenocarcinoma: challenges and opportunities. Drug. Deliv. Transl. Res. https://doi.org/10.1007/s13346-025-01908-7 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sethna, Z. et al. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature 639, 1042–1051 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sahin, U. et al. Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC. Nature https://doi.org/10.1038/s41586-025-10004-2 (2026).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT04560790 (2022).

  • Lee, R. G. et al. Efficacy and safety of an investigational single-course CRISPR base-editing therapy targeting PCSK9 in nonhuman primate and mouse models. Circulation 147, 242–253 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Musunuru, K. et al. In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates. Nature 593, 429–434 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kabadi, A. M. et al. AAV-based CRISPR–Cas9 genome editing: challenges and engineering opportunities. Curr. Opin. Biomed. Eng. 29, 100517 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Anzalone, A. V., Koblan, L. W. & Liu, D. R. Genome editing with CRISPR–Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 38, 824–844 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bara-Ledesma, N. et al. Advances in gene therapy for rare diseases: targeting functional haploinsufficiency through AAV and mRNA approaches. Int. J. Mol. Sci. 26, 578 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Colella, P., Ronzitti, G. & Mingozzi, F. Emerging issues in AAV-mediated in vivo gene therapy. Mol. Ther. Methods Clin. Dev. 8, 87–104 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Villiger, L. et al. In vivo cytidine base editing of hepatocytes without detectable off-target mutations in RNA and DNA. Nat. Biomed. Eng. 5, 179–189 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Popovitz, J. et al. Gene editing therapeutics based on mRNA delivery. Adv. Drug. Delivery Rev. 200, 115026 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Sundararaman, S. S., Döring, Y. & van der Vorst, E. P. C. PCSK9: a multi-faceted protein that is involved in cardiovascular biology. Biomedicines 9, 793 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Di Taranto, M. D. et al. Identification and in vitro characterization of two new PCSK9 gain of function variants found in patients with familial hypercholesterolemia. Sci. Rep. 7, 15282 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, H., Krauss, R. M., Chang, J. T. & Teng, B.-B. PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and endothelial dysfunction. J. Lipid Res. 59, 207–223 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Katzmann, J. L., Gouni-Berthold, I. & Laufs, U. PCSK9 inhibition: insights from clinical trials and future prospects. Front. Physiol. 11, 595819 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kasiewicz, L. N. et al. GalNAc–lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat. Commun. 14, 2776 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wan, P. et al. In vivo base editing gene therapy for heterozygous familial hypercholesterolemia: a phase 1 trial. Nat. Med. https://doi.org/10.1038/s41591-026-04254-4 (2026).

    Article 
    PubMed 

    Google Scholar
     

  • Fitzgerald, K. et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N. Engl. J. Med. 376, 41–51 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Musunuru, K. et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2504747 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marks, P. Progress in the development of N-of-1 therapy. N. Engl. J. Med. https://doi.org/10.1056/NEJMe2505704 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Gropman, A. L. & Komor, A. C. Personalized gene editing to treat an inborn error of metabolism. N. Engl. J. Med. https://doi.org/10.1056/NEJMe2505721 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Summar, M. L. et al. The incidence of urea cycle disorders. Mol. Genet. Metab. 110, 179–180 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kido, J., Matsumoto, S., Sugawara, K., Sawada, T. & Nakamura, K. Variants associated with urea cycle disorders in Japanese patients: nationwide study and literature review. Am. J. Med. Genet. Pt A 185, 2026–2036 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Diorio, C. et al. BEAM-201 for the treatment of relapsed and/or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LL): initial data from the phase (Ph) 1/2 dose-exploration, dose-expansion, safety, and efficacy study of multiplex base-edited allogeneic anti-CD7 CAR-T-cells. Blood 144, 4838 (2024).

    Article 

    Google Scholar
     

  • Chen, P. J. & Liu, D. R. Prime editing for precise and highly versatile genome manipulation. Nat. Rev. Genet. 24, 161–177 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, S. et al. Payload distribution and capacity of mRNA lipid nanoparticles. Nat. Commun. 13, 5561 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, X. et al. Harnessing eukaryotic retroelement proteins for transgene insertion into human safe-harbor loci. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02137-y (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, Y. et al. All-RNA-mediated targeted gene integration in mammalian cells with rationally engineered R2 retrotransposons. Cell 187, 4674–4689.e18 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yarnall, M. T. N. et al. Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases. Nat. Biotechnol. 41, 500–512 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Breda, L. et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science 381, 436–443 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Frangoul, H. et al. CRISPR–Cas9 gene editing for sickle cell disease and β-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Breda, L. et al. In vivo modification of hematopoietic stem cells by targeted lipid nanoparticles encapsulating mRNA. Blood 140, 305–306 (2022).

    Article 

    Google Scholar
     

  • Shi, D., Toyonaga, S. & Anderson, D. G. In vivo RNA delivery to hematopoietic stem and progenitor cells via targeted lipid nanoparticles. Nano Lett. 23, 2938–2944 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Masson, G. Vertex pays Orna $65M to work on next-gen gene therapies for blood disorders. Fierce Biotech https://www.fiercebiotech.com/biotech/vertex-pays-orna-65m-work-next-gen-gene-therapies-blood-disorders (7 January 2025).

  • Lian, X. et al. Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells. Nat. Nanotechnol. 19, 1409–1417 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xue, L. et al. Rational design of bisphosphonate lipid-like materials for mRNA delivery to the bone microenvironment. J. Am. Chem. Soc. 144, 9926–9937 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hofstraat, S. R. J. et al. Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors. Nat. Nanotechnol. https://doi.org/10.1038/s41565-024-01847-3 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Amabile, A. et al. Bispecific antibody targeting of lipid nanoparticles. Preprint at bioRxiv https://doi.org/10.1101/2024.12.20.629467 (2024).

  • Herrera-Barrera, M. et al. Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates. Sci. Adv. 9, eadd4623 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Han, E. L. et al. Peptide-functionalized lipid nanoparticles for targeted systemic mRNA delivery to the brain. Nano Lett. 25, 800–810 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Akinc, A. et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol. Ther. 18, 1357–1364 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Khorev, O., Stokmaier, D., Schwardt, O., Cutting, B. & Ernst, B. Trivalent, Gal/GalNAc-containing ligands designed for the asialoglycoprotein receptor. Bioorg. Med. Chem. 16, 5216–5231 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tanowitz, M. et al. Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine-conjugated and unconjugated phosphorothioate antisense oligonucleotides into liver hepatocytes. Nucleic Acids Res. 45, 12388–12400 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nair, J. K. et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing. J. Am. Chem. Soc. 136, 16958–16961 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Melamed, J. R. et al. Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer. Sci. Adv. 9, eade1444 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, J. et al. Lipid nanoparticle-mediated lymph node-targeting delivery of mRNA cancer vaccine elicits robust CD8+ T cell response. Proc. Natl Acad. Sci. USA 119, e2207841119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nakamura, T. & Harashima, H. Dawn of lipid nanoparticles in lymph node targeting: potential in cancer immunotherapy. Adv. Drug. Delivery Rev. 167, 78–88 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Lin, L. et al. Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma. Leukemia 35, 752–763 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Granit, V. et al. Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. Lancet Neurol. 22, 578–590 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vu, T. et al. BCMA-directed mRNA CAR T cell therapy for myasthenia gravis: a randomized, double-blind, placebo-controlled phase 2b trial. Nat. Med. 32, 1131–1141 (2026).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meister, H. et al. Multifunctional mRNA-based CAR T cells display promising antitumor activity against glioblastoma. Clin. Cancer Res. 28, 4747–4756 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mackensen, A. et al. CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. Nat. Med. 29, 2844–2853 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Foster, J. B. et al. Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors. J. Immunother. Cancer 10, e004450 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baker, D. J., Arany, Z., Baur, J. A., Epstein, J. A. & June, C. H. CAR T therapy beyond cancer: the evolution of a living drug. Nature 619, 707–715 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Billingsley, M. M. et al. Orthogonal design of experiments for optimization of lipid nanoparticles for mRNA engineering of CAR T cells. Nano Lett. 22, 533–542 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tombácz, I. et al. Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA–LNPs. Mol. Ther. 29, 3293–3304 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Billingsley, M. M. et al. In vivo mRNA CAR T cell engineering via targeted ionizable lipid nanoparticles with extrahepatic tropism. Small 20, 2304378 (2024).

    Article 
    CAS 

    Google Scholar
     

  • Hunter, T. L. et al. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science 388, 1311–1317 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bae, S.-H. et al. A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety. Bioact. Mater. 38, 486–498 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nogueira, S. S. et al. Polysarcosine-functionalized lipid nanoparticles for therapeutic mRNA delivery. ACS Appl. Nano Mater. 3, 10634–10645 (2020).

    Article 
    CAS 

    Google Scholar
     

  • Kang, D. D. et al. Engineering LNPs with polysarcosine lipids for mRNA delivery. Bioact. Mater. 37, 86–93 (2024).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tenchov, R., Sasso, J. M. & Zhou, Q. A. PEGylated lipid nanoparticle formulations: immunological safety and efficiency perspective. Bioconjugate Chem. 34, 941–960 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Bigini, P. et al. The role and impact of polyethylene glycol on anaphylactic reactions to COVID-19 nano-vaccines. Nat. Nanotechnol. 16, 1169–1171 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baiersdörfer, M. et al. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol. Ther. Nucleic Acids 15, 26–35 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piao, X. et al. Double-stranded RNA reduction by chaotropic agents during in vitro transcription of messenger RNA. Mol. Ther. Nucleic Acids 29, 618–624 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dousis, A., Ravichandran, K., Hobert, E. M., Moore, M. J. & Rabideau, A. E. An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts. Nat. Biotechnol. 41, 560–568 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Martínez, J., Lampaya, V., Larraga, A., Magallón, H. & Casabona, D. Purification of linearized template plasmid DNA decreases double-stranded RNA formation during IVT reaction. Front. Mol. Biosci. 10, 1248511 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Krienke, C. et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 371, 145–153 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, Q. et al. Use of a liver-targeting nanoparticle platform to intervene in peanut-induced anaphylaxis through delivery of an Ara h2 T-cell epitope. Nano Today 42, 101370 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cao, W. & Xia, T. mRNA lipid nanoparticles induce immune tolerance to treat human diseases. Med. Rev. 3, 180–183 (2021).

    Article 

    Google Scholar
     

  • Vaidyanathan, S. et al. Uridine depletion and chemical modification increase Cas9 mRNA activity and reduce immunogenicity without HPLC purification. Mol. Ther. Nucleic Acids 12, 530–542 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Presnyak, V. et al. Codon optimality is a major determinant of mRNA stability. Cell 160, 1111–1124 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boccaletto, P. et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 50, D231–D235 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nelson, J. et al. Impact of mRNA chemistry and manufacturing process on innate immune activation. Sci. Adv. 6, eaaz6893 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meulewaeter, S. et al. Continuous freeze-drying of messenger RNA lipid nanoparticles enables storage at higher temperatures. J. Control. Rel. 357, 149–160 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Bogaert, B. et al. A lipid nanoparticle platform for mRNA delivery through repurposing of cationic amphiphilic drugs. J. Control. Rel. 350, 256–270 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Da Silva Sanchez, A. J. et al. Substituting racemic ionizable lipids with stereopure ionizable lipids can increase mRNA delivery. J. Control. Rel. 353, 270–277 (2023).

    Article 

    Google Scholar
     

  • Ning, H. et al. Rational design of microRNA-responsive switch for programmable translational control in mammalian cells. Nat. Commun. 14, 7193 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Masaki, K., Fujita, Y. & Saito, H. microRNA-responsive ON–OFF hybrid mRNA switch for precise protein expression control. Mol. Ther. Nucleic Acids 36, 102609 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Abe, I., Ohno, H., Mochizuki, M., Hayashi, K. & Saito, H. Split RNA switch orchestrates pre- and post-translational control to enable cell type-specific gene expression. Nat. Commun. 16, 5362 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, X. et al. Oral delivery of liquid mRNA therapeutics by an engineered capsule for treatment of preclinical intestinal disease. Sci. Transl. Med. 17, eadu1493 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Macht, A. et al. Mucosal IFNλ1 mRNA-based immunomodulation effectively reduces SARS-CoV-2 induced mortality in mice. EMBO Rep. 25, 3777–3788 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sinegra, A. J., Evangelopoulos, M., Park, J., Huang, Z. & Mirkin, C. A. Lipid nanoparticle spherical nucleic acids for intracellular DNA and RNA delivery. Nano Lett. 21, 6584–6591 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Semple, S. C., Leone, R., Barbosa, C. J., Tam, Y. K. & Lin, P. J. C. Lipid nanoparticle delivery systems to enable mRNA-based therapeutics. Pharmaceutics 14, 398 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • LoPresti, S. T., Arral, M. L., Chaudhary, N. & Whitehead, K. A. The replacement of helper lipids with charged alternatives in lipid nanoparticles facilitates targeted mRNA delivery to the spleen and lungs. J. Control. Rel. 345, 819–831 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Dahlman, J. E. et al. Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics. Proc. Natl Acad. Sci. USA 114, 2060–2065 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, H. et al. Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys. Nat. Biotechnol. 43, 1813–1820 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Haley, R. M. et al. Lipid nanoparticles for in vivo lung delivery of CRISPR–Cas9 ribonucleoproteins allow gene editing of clinical targets. ACS Nano 19, 13790–13804 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cappelluti, M. A. et al. Durable and efficient gene silencing in vivo by hit-and-run epigenome editing. Nature 627, 416–423 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hennig, M. et al. Inhaled DNAI1 mRNA therapy for treatment of primary ciliary dyskinesia. Proc. Natl Acad. Sci. USA 122, e2421915122 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cohn, D. M. et al. CRISPR-based therapy for hereditary angioedema. N. Engl. J. Med. 392, 458–467 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, R. et al. Engineering circular RNA for enhanced protein production. Nat. Biotechnol. 41, 262–272 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McKay, P. F. et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat. Commun. 11, 3523 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pollock, K. M. et al. Safety and immunogenicity of a self-amplifying RNA vaccine against COVID-19: COVAC1, a phase I, dose-ranging trial. eClinicalMedicine 44, 101262 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Trepotec, Z., Geiger, J., Plank, C., Aneja, M. K. & Rudolph, C. Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life. RNA 25, 507–518 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vogel, A. B. et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol. Ther. 26, 446–455 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06714253 (2026).

  • Papukashvili, D. et al. Self-amplifying RNA approach for protein replacement therapy. IJMS 23, 12884 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ballesteros-Briones, M. C., Silva-Pilipich, N., Herrador-Cañete, G., Vanrell, L. & Smerdou, C. A new generation of vaccines based on alphavirus self-amplifying RNA. Curr. Opin. Virol. 44, 145–153 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, J., Eygeris, Y., Gupta, M. & Sahay, G. Self-assembled mRNA vaccines. Adv. Drug. Delivery Rev. 170, 83–112 (2021).

    Article 
    CAS 

    Google Scholar
     

  • Maruggi, G., Zhang, C., Li, J., Ulmer, J. B. & Yu, D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol. Ther. 27, 757–772 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bloom, K., van den Berg, F. & Arbuthnot, P. Self-amplifying RNA vaccines for infectious diseases. Gene Ther. 28, 117–129 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pepini, T. et al. Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design. J. Immunol. 198, 4012–4024 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torkzaban, B. et al. Use of polyadenosine tail mimetics to enhance mRNA expression from genes associated with haploinsufficiency disorders. Mol. Ther. Nucleic Acids 36, 102453 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, H. et al. Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation. Nat. Biotechnol. 43, 1128–1143 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Jin, L., Zhou, Y., Zhang, S. & Chen, S.-J. mRNA vaccine sequence and structure design and optimization: advances and challenges. J. Biol. Chem. 301, 108015 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fu, H. et al. Codon optimization with deep learning to enhance protein expression. Sci. Rep. 10, 17617 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Constant, D. A. et al. Deep learning-based codon optimization with large-scale synonymous variant datasets enables generalized tunable protein expression. Preprint at bioRxiv https://doi.org/10.1101/2023.02.11.528149 (2023).

  • Zhang, H. et al. Deep generative models design mRNA sequences with enhanced translational capacity and stability. Science 390, eadr8470 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, Z. & Dong, Y. AI-powered design accelerates the development of mRNA therapeutics. Nat. Chem. Biol. 22, 15–16 (2026).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Castillo-Hair, S. et al. Optimizing 5′UTRs for mRNA-delivered gene editing using deep learning. Nat. Commun. 15, 5284 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y., Gao, J., Zhang, X. & Fang, X. Joint Design of 5′ Untranslated Region and Coding Sequence of mRNA. Preprint at arXiv https://doi.org/10.48550/arXiv.2410.20781 (2024).

  • Luna-Cerralbo, D. et al. A statistical-physics approach for codon usage optimisation. Comput. Struct. Biotechnol. J. 23, 3050–3064 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Madani, A. et al. Large language models generate functional protein sequences across diverse families. Nat. Biotechnol. 41, 1099–1106 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wayment-Steele, H. K. et al. Theoretical basis for stabilizing messenger RNA through secondary structure design. Nucleic Acids Res. 49, 10604–10617 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vostrosablin, N. et al. mRNAid, an open-source platform for therapeutic mRNA design and optimization strategies. NAR Genom. Bioinform. 6, lqae028 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lai, W.-J. C. et al. Intrinsically unstructured sequences in the mRNA 3′ UTR reduce the ability of poly(A) tail to enhance translation. J. Mol. Biol. 434, 167877 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Haberman, N. et al. Widespread 3′UTR capped RNAs derive from G-rich regions in proximity to AGO2 binding sites. BMC Biol. 22, 254 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carbonell-Sala, S. et al. CapTrap-seq: a platform-agnostic and quantitative approach for high-fidelity full-length RNA sequencing. Nat. Commun. 15, 5278 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, Y. et al. AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery. Nat. Commun. 15, 6305 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     



  • Read More

    Leave a comment