Tailor made: the art of therapeutic mRNA design

Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R. & Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840–854 (2022).

Article  CAS  PubMed  Google Scholar 

Lindsay, K. E. et al. Visualization of early events in mRNA vaccine delivery in non-human primates via PET–CT and near-infrared imaging. Nat. Biomed. Eng. 3, 371–380 (2019).

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 

Meyer, R. A., Neshat, S. Y., Green, J. J., Santos, J. L. & Tuesca, A. D. Targeting strategies for mRNA delivery. Mater. Today Adv. 14, 100240 (2022).

Article  CAS  Google Scholar 

Paunovska, K., Loughrey, D. & Dahlman, J. E. Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 23, 265–280 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morris, C., Cluet, D. & Ricci, E. P. Ribosome dynamics and mRNA turnover, a complex relationship under constant cellular scrutiny. Wiley Iinterdiscip. Rev. RNA 12, e1658 (2021).

Article  CAS  PubMed  Google Scholar 

Mercier, B. C. et al. Translation-dependent and independent mRNA decay occur through mutually exclusive pathways that are defined by ribosome density during T cell activation. Preprint at bioRxiv https://doi.org/10.1101/2020.10.16.341222 (2020).

Villanueva, J. C. How Many Atoms Are There in the Universe? Universe Today https://www.universetoday.com/36302/atoms-in-the-universe/ (2009).

Hanson, G. & Coller, J. Codon optimality, bias and usage in translation and mRNA decay. Nat. Rev. Mol. Cell Biol. 19, 20–30 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Hanson, G., Alhusaini, N., Morris, N., Sweet, T. & Coller, J. Translation elongation and mRNA stability are coupled through the ribosomal A-site. RNA 24, 1377–1389 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bae, H. & Coller, J. Codon optimality-mediated mRNA degradation: linking translational elongation to mRNA stability. Mol. Cell 82, 1467–1476 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zolotukhin, S., Potter, M., Hauswirth, W. W., Guy, J. & Muzyczka, N. A ‘humanized’ green fluorescent protein cDNA adapted for high-level expression in mammalian cells. J. Virol. 70, 4646–4654 (1996).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kudla, G., Lipinski, L., Caffin, F., Helwak, A. & Zylicz, M. High guanine and cytosine content increases mRNA levels in mammalian cells. PLoS Biol. 4, e180 (2006).

Article  PubMed  PubMed Central  Google Scholar 

Mordstein, C. et al. Codon usage and splicing jointly influence mRNA localization. Cell Syst. 10, 351–362.e8 (2020).

Article  CAS  PubMed  PubMed Central  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 

Parvathy, S. T., Udayasuriyan, V. & Bhadana, V. Codon usage bias. Mol. Biol. Rep. 49, 539–565 (2022).

Article  CAS  PubMed  Google Scholar 

Sharp, P. M. & Li, W. H. The codon adaptation index—a measure of directional synonymous codon usage bias, and its potential applications. Nucleic Acids Res. 15, 1281–1295 (1987).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Reis, M., dos, Savva, R. & Wernisch, L. Solving the riddle of codon usage preferences: a test for translational selection. Nucleic Acids Res. 32, 5036–5044 (2004).

Article  PubMed  PubMed Central  Google Scholar 

Forrest, M. E. et al. Codon and amino acid content are associated with mRNA stability in mammalian cells. PLoS ONE 15, e0228730 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dittmar, K. A., Goodenbour, J. M. & Pan, T. Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2, e221 (2006).

Article  PubMed  PubMed Central  Google Scholar 

Pinkard, O., McFarland, S., Sweet, T. & Coller, J. Quantitative tRNA-sequencing uncovers metazoan tissue-specific tRNA regulation. Nat. Commun. 11, 4104 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tuller, T. et al. An evolutionarily conserved mechanism for controlling the efficiency of protein translation. Cell 141, 344–354 (2010).

Article  CAS  PubMed  Google Scholar 

Sejour, R., Leatherwood, J., Yurovsky, A. & Futcher, B. No ramp needed: spandrels, statistics, and a slippery slope. eLife 12, RP89656 (2023).

Google Scholar 

Mortimer, S. A., Kidwell, M. A. & Doudna, J. A. Insights into RNA structure and function from genome-wide studies. Nat. Rev. Genet. 15, 469–479 (2014).

Article  CAS  PubMed  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 

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 

Tanzer, A., Hofacker, I. L. & Lorenz, R. RNA modifications in structure prediction – status quo and future challenges. Methods 156, 32–39 (2019).

Article  CAS  PubMed  Google Scholar 

Mauger, D. M. et al. mRNA structure regulates protein expression through changes in functional half-life. Proc. Natl Acad. Sci. USA 116, 24075–24083 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kierzek, E. et al. Secondary structure prediction for RNA sequences including N6-methyladenosine. Nat. Commun. 13, 1271 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Turner, D. H., Sugimoto, N. & Freier, S. M. RNA structure prediction. Annu. Rev. Biophys. Biophys. Chem. 17, 167–192 (1988).

Article  CAS  PubMed  Google Scholar 

Turner, D. H. Thermodynamics of base pairing. Curr. Opin. Struct. Biol. 6, 299–304 (1996).

Article  CAS  PubMed  Google Scholar 

Pleij, C. W., Rietveld, K. & Bosch, L. A new principle of RNA folding based on pseudoknotting. Nucleic Acids Res. 13, 1717–1731 (1985).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zuber, J., Schroeder, S. J., Sun, H., Turner, D. H. & Mathews, D. H. Nearest neighbor rules for RNA helix folding thermodynamics: improved end effects. Nucleic Acids Res. 50, 5251–5262 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xia, T. et al. Thermodynamic parameters for an expanded nearest-neighbor model for formation of RNA duplexes with Watson−Crick base pairs. Biochemistry 37, 14719–14735 (1998).

Article  CAS  PubMed  Google Scholar 

Andronescu, M., Condon, A., Turner, D. H. & Mathews, D. H. The determination of RNA folding nearest neighbor parameters. Methods Mol. Biol. 1097, 45–70 (2014).

Article  CAS  PubMed  Google Scholar 

Raden, M., Mohamed, M. M., Ali, S. M. & Backofen, R. Interactive implementations of thermodynamics-based RNA structure and RNA–RNA interaction prediction approaches for example-driven teaching. PLOS Comput. Biol. 14, e1006341 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Hofacker, I. L., Schuster, P. & Stadler, P. F. Combinatorics of RNA secondary structures. Discret. Appl. Math. 88, 207–237 (1998).

Article  Google Scholar 

Mathews, D. H. Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization. RNA 10, 1178–1190 (2004).

Article  CAS  PubMed 

Comments (0)

No login
gif