DNA and RNA chemical modifications play a major role in the functioning of cells both in the normal and pathological context. Epigenetic and epitranscriptomic are fields in which a molecular point of view is required to understand the physiology of biological systems. We will combine our expertise[i] to propose new analytical (MS, NMR), structural (Crystallography, CryoEM, molecular modelling) or functional (chemical probes, enzymatic assays) approaches to characterize (in vitro, ex and in vivo) these chemical modifications, their regulation network, and understand their impact on cellular homeostasis with potential for new therapeutic approaches. We also develop chemical or enzymatic technologies to scale up the production of heavily modified oligonucleotides as tools (catalysts, sensors) or for therapeutic purposes (vaccines).[ii]
[i] a) Smoczynski, J. et al, Acc Chem Res. 2024, 57, 429-438 (https://doi.org/10.1021/acs.accounts.3c00568). b) Nardella, F. et al, ACS Cent. Sci. 2020, 6, 16-21 (https://doi.org/10.1021/acscentsci.9b00874). c) Saaidi, A. et al, Nucl. Acid. Res. 2020, 48, 8276-8289 (https://doi.org/10.1093/nar/gkaa607). d) McKenzie, L. et al, Chem. Soc. Rev. 2021, 50, 5126-5164 (https://doi.org/10.1039/D0CS01430C). e) Meynier, V. et al, Nucl. Acid. Res. 2022, 50, 5793-5806 (https://doi.org/10.1093/nar/gkac354). f) Meynier V. et al, Nature Comm 2024, 15, 4683 (https://doi: 10.1038/s41467-024-49132-0). g) Puyo-Fourtine, J. et al J. Phys. Chem. B. 2022, 126(22), 4022-4034 (https://doi.org/10.1021/acs.jpcb.2c01158). h) Arruda, D. C. et al, J. Control Release, 2022, 350, 228-243 (https://doi.org/10.1016/j.jconrel.2022.08.030).
[ii] Martinez P et al. Microorganisms 2023 (doi: 10.3390/microorganisms11020241)