{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:41:27Z","timestamp":1792453287140,"version":"4.5.0"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Chem Eng"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>RNA droplets assembled from cotranscriptionally folded nanostructures have recently emerged as a promising platform for constructing protocells and minimal synthetic cell models. A custom-designed DNA template encodes an RNA nanostar that self-assembles into droplets by kissing-loop interactions. Here we show that such RNA droplets encapsulate their DNA template, creating a genotype\u2013phenotype link. We find that low mutation rates in the DNA template increase the phenotypical and functional complexity of the RNA droplets. Surprisingly, mutagenesis leads to the formation of long-lived vacuoles. With theory and next-generation sequencing, we explain this emergent behavior. We identify mutant nanostars that facilitate the formation of vacuoles through altered interactions between nanostars. Strikingly, vacuolated droplets exhibit micrometer-scale movement driven by internal vacuole dynamics \u2013 an emergent function resulting from mutagenesis. Beyond motility, we show that the vacuoles can be used as subcompartments to store cargo in the RNA droplets. Our findings establish RNA droplets as self-contained, evolvable systems, opening new avenues for the bottom-up evolution of synthetic cells and origins-of-life research.<\/jats:p>","DOI":"10.1038\/s44286-026-00454-4","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:02:44Z","timestamp":1791363764000},"page":"573-583","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic encoding and mutagenesis of RNA droplet phenotypes"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4458-9579","authenticated-orcid":false,"given":"William","family":"Verstraeten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai P.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Taskina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranay","family":"Jaiswal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9931-3741","authenticated-orcid":false,"given":"Ivar S.","family":"Haugerud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Helbig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Hamberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-887X","authenticated-orcid":false,"given":"Michael","family":"Platten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-0405","authenticated-orcid":false,"given":"Christoph A.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2115-3551","authenticated-orcid":false,"given":"Kerstin","family":"G\u00f6pfrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"454_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/35053176","volume":"409","author":"JW Szostak","year":"2001","unstructured":"Szostak, J. W., Bartel, D. P. & Luisi, P. L. Synthesizing life. Nature 409, 387\u2013390 https:\/\/doi.org\/10.1038\/35053176 (2001).","journal-title":"Nature"},{"key":"454_CR2","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1126\/science.1211701","volume":"333","author":"P Schwille","year":"2011","unstructured":"Schwille, P. Bottom-up synthetic biology: engineering in a tinkerer\u2019s world. Science 333, 1252\u20131254 https:\/\/doi.org\/10.1126\/science.1211701 (2011).","journal-title":"Science"},{"key":"454_CR3","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.tibtech.2018.03.008","volume":"36","author":"K G\u00f6pfrich","year":"2018","unstructured":"G\u00f6pfrich, K., Platzman, I. & Spatz, J. P. Mastering complexity: towards bottom-up construction of multifunctional eukaryotic synthetic cells. Trends Biotechnol 36, 938\u2013951 https:\/\/doi.org\/10.1016\/j.tibtech.2018.03.008 (2018).","journal-title":"Trends Biotechnol"},{"key":"454_CR4","doi-asserted-by":"publisher","first-page":"102399","DOI":"10.1016\/j.chempr.2024.102399","volume":"11","author":"CME Kriebisch","year":"2025","unstructured":"Kriebisch, C. M. E. et al. A roadmap toward the synthesis of life. Chem 11, 102399 https:\/\/doi.org\/10.1016\/j.chempr.2024.102399 (2025).","journal-title":"Chem"},{"key":"454_CR5","doi-asserted-by":"publisher","first-page":"7514","DOI":"10.1073\/pnas.062710399","volume":"99","author":"T Matsuura","year":"2002","unstructured":"Matsuura, T. et al. Importance of compartment formation for a self-encoding system. Proc. Natl Acad. Sci. USA 99, 7514\u20137517 https:\/\/doi.org\/10.1073\/pnas.062710399 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"454_CR6","doi-asserted-by":"publisher","first-page":"3507","DOI":"10.1021\/acssynbio.1c00430","volume":"10","author":"H Okauchi","year":"2021","unstructured":"Okauchi, H. & Ichihashi, N. Continuous Cell-Free Replication and Evolution of Artificial Genomic DNA in a Compartmentalized Gene Expression System. ACS Synth. Biol. 10, 3507\u20133517 https:\/\/doi.org\/10.1021\/acssynbio.1c00430 (2021).","journal-title":"ACS Synth. Biol."},{"key":"454_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3494","volume":"4","author":"N Ichihashi","year":"2013","unstructured":"Ichihashi, N. et al. Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment. Nat. Commun. 4, 2494 https:\/\/doi.org\/10.1038\/ncomms3494 (2013).","journal-title":"Nat. Commun."},{"key":"454_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53226-0","volume":"15","author":"Z Abil","year":"2024","unstructured":"Abil, Z. et al. Darwinian Evolution of Self-Replicating DNA in a Synthetic Protocell. Nat. Commun. 15, 9091 https:\/\/doi.org\/10.1038\/s41467-024-53226-0 (2024).","journal-title":"Nat. Commun."},{"key":"454_CR9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/msb4100090","volume":"2","author":"AC Forster","year":"2006","unstructured":"Forster, A. C. & Church, G. M. Towards synthesis of a minimal cell. Mol. Syst. Biol. 2, 45 https:\/\/doi.org\/10.1038\/msb4100090 (2006).","journal-title":"Mol. Syst. Biol."},{"key":"454_CR10","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1021\/acs.biochem.3c00023","volume":"62","author":"J De Capitani","year":"2023","unstructured":"De Capitani, J. & Mutschler, H. The long road to a synthetic self-replicating central dogma. Biochemistry 62, 1221\u20131232 https:\/\/doi.org\/10.1021\/acs.biochem.3c00023 (2023).","journal-title":"Biochemistry"},{"key":"454_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17863-5","volume":"11","author":"D Blanken","year":"2020","unstructured":"Blanken, D., Foschepoth, D., Serr\u00e3o, A. C. & Danelon, C. Genetically controlled membrane synthesis in liposomes. Nat. Commun. 11, 4317 https:\/\/doi.org\/10.1038\/s41467-020-17863-5 (2020).","journal-title":"Nat. Commun."},{"key":"454_CR12","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1038\/s42003-022-03999-1","volume":"5","author":"S Eto","year":"2022","unstructured":"Eto, S. et al. Phospholipid synthesis inside phospholipid membrane vesicles. Commun. Biol. 5, 1016 https:\/\/doi.org\/10.1038\/s42003-022-03999-1 (2022).","journal-title":"Commun. Biol."},{"key":"454_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24772-8","volume":"12","author":"L Olivi","year":"2021","unstructured":"Olivi, L. et al. Towards a synthetic cell cycle. Nat. Commun. 12, 4531 https:\/\/doi.org\/10.1038\/s41467-021-24772-8 (2021).","journal-title":"Nat. Commun."},{"key":"454_CR14","doi-asserted-by":"publisher","first-page":"eaba3471","DOI":"10.1126\/sciadv.aba3471","volume":"6","author":"Y Sato","year":"2020","unstructured":"Sato, Y., Sakamoto, T. & Takinoue, M. Sequence-based engineering of dynamic functions of micrometer-sized DNA droplets. Sci. Adv. 6, eaba3471 https:\/\/doi.org\/10.1126\/sciadv.aba3471 (2020).","journal-title":"Sci. Adv."},{"key":"454_CR15","doi-asserted-by":"publisher","first-page":"2202711","DOI":"10.1002\/smll.202202711","volume":"19","author":"MP Tran","year":"2023","unstructured":"Tran, M. P. et al. A DNA segregation module for synthetic cells. Small 19, 2202711 https:\/\/doi.org\/10.1002\/smll.202202711 (2023).","journal-title":"Small"},{"key":"454_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51299-5","volume":"15","author":"T Maruyama","year":"2024","unstructured":"Maruyama, T., Gong, J. & Takinoue, M. Temporally controlled multistep division of DNA droplets for dynamic artificial cells. Nat. Commun. 15, 7397 https:\/\/doi.org\/10.1038\/s41467-024-51299-5 (2024).","journal-title":"Nat. Commun."},{"key":"454_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18815-9","volume":"11","author":"C Donau","year":"2020","unstructured":"Donau, C. et al. Active coacervate droplets as a model for membraneless organelles and protocells. Nat. Commun. 11, 5167 https:\/\/doi.org\/10.1038\/s41467-020-18815-9 (2020).","journal-title":"Nat. Commun."},{"key":"454_CR18","doi-asserted-by":"publisher","first-page":"064601","DOI":"10.1088\/1361-6633\/ab052b","volume":"82","author":"CA Weber","year":"2019","unstructured":"Weber, C. A., Zwicker, D., J\u00fclicher, F. & Lee, C. F. Physics of active emulsions. Rep. Prog. Phys. 82, 064601 https:\/\/doi.org\/10.1088\/1361-6633\/ab052b (2019).","journal-title":"Rep. Prog. Phys."},{"key":"454_CR19","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/nphys3984","volume":"13","author":"D Zwicker","year":"2017","unstructured":"Zwicker, D., Seyboldt, R., Weber, C. A., Hyman, A. A. & J\u00fclicher, F. Growth and division of active droplets provides a model for protocells. Nat. Phys. 13, 408\u2013413 https:\/\/doi.org\/10.1038\/nphys3984 (2017).","journal-title":"Nat. Phys."},{"key":"454_CR20","doi-asserted-by":"publisher","first-page":"2200132","DOI":"10.1002\/andp.202200132","volume":"534","author":"J Bauermann","year":"2022","unstructured":"Bauermann, J., Weber, C. A. & J\u00fclicher, F. Energy and matter supply for active droplets. Ann. Phys. 534, 2200132 https:\/\/doi.org\/10.1002\/andp.202200132 (2022).","journal-title":"Ann. Phys."},{"key":"454_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59456-0","volume":"16","author":"S Majumder","year":"2025","unstructured":"Majumder, S., Coupe, S., Fakhri, N. & Jain, A. Sequence-encoded intermolecular base pairing modulates fluidity in DNA and RNA condensates. Nat. Commun. 16, 4258 https:\/\/doi.org\/10.1038\/s41467-025-59456-0 (2025).","journal-title":"Nat. Commun."},{"key":"454_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30158-1","volume":"13","author":"D Wollny","year":"2022","unstructured":"Wollny, D. et al. Characterization of RNA content in individual phase-separated coacervate microdroplets. Nat. Commun. 13, 2626 https:\/\/doi.org\/10.1038\/s41467-022-30158-1 (2022).","journal-title":"Nat. Commun."},{"key":"454_CR23","doi-asserted-by":"publisher","first-page":"20230021","DOI":"10.1098\/rsfs.2023.0021","volume":"13","author":"M Takinoue","year":"2023","unstructured":"Takinoue, M. DNA droplets for intelligent and dynamical artificial cells: from the viewpoint of computation and non-equilibrium systems. Interface Focus 13, 20230021 https:\/\/doi.org\/10.1098\/rsfs.2023.0021 (2023).","journal-title":"Interface Focus"},{"key":"454_CR24","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/s41570-024-00606-1","volume":"8","author":"A Samanta","year":"2024","unstructured":"Samanta, A., Baranda Pellejero, L., Masukawa, M. & Walther, A. DNA-empowered synthetic cells as minimalistic life forms. Nat. Rev. Chem. 8, 454\u2013470 https:\/\/doi.org\/10.1038\/s41570-024-00606-1 (2024).","journal-title":"Nat. Rev. Chem."},{"key":"454_CR25","doi-asserted-by":"publisher","first-page":"e202412534","DOI":"10.1002\/anie.202412534","volume":"63","author":"AL Holtmannsp\u00f6tter","year":"2024","unstructured":"Holtmannsp\u00f6tter, A. L. et al. Regulating nucleic acid catalysis using active droplets. Angew. Chem. Int. Ed. 63, e202412534 https:\/\/doi.org\/10.1002\/anie.202412534 (2024).","journal-title":"Angew. Chem. Int. Ed."},{"key":"454_CR26","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1016\/j.chempr.2023.10.004","volume":"9","author":"L Malouf","year":"2023","unstructured":"Malouf, L. et al. Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity. Chem 9, 3347\u20133364 https:\/\/doi.org\/10.1016\/j.chempr.2023.10.004 (2023).","journal-title":"Chem"},{"key":"454_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57770-1","volume":"16","author":"M Wang","year":"2025","unstructured":"Wang, M. et al. Responsive DNA artificial cells for contact and behavior regulation of mammalian cells. Nat. Commun. 16, 2410 https:\/\/doi.org\/10.1038\/s41467-025-57770-1 (2025).","journal-title":"Nat. Commun."},{"key":"454_CR28","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s42004-024-01185-4","volume":"7","author":"W Liu","year":"2024","unstructured":"Liu, W., Deng, J., Song, S., Sethi, S. & Walther, A. A facile DNA coacervate platform for engineering wetting, engulfment, fusion and transient behavior. Commun. Chem. 7, 100 https:\/\/doi.org\/10.1038\/s42004-024-01185-4 (2024).","journal-title":"Commun. Chem."},{"key":"454_CR29","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1038\/s41565-024-01726-x","volume":"19","author":"G Fabrini","year":"2024","unstructured":"Fabrini, G. et al. Co-transcriptional production of programmable RNA condensates and synthetic organelles. Nat. Nanotechnol. 19, 1665\u20131673 https:\/\/doi.org\/10.1038\/s41565-024-01726-x (2024).","journal-title":"Nat. Nanotechnol."},{"key":"454_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50003-x","volume":"15","author":"JM Stewart","year":"2024","unstructured":"Stewart, J. M. et al. Modular RNA motifs for orthogonal phase separated compartments. Nat. Commun. 15, 6244 https:\/\/doi.org\/10.1038\/s41467-024-50003-x (2024).","journal-title":"Nat. Commun."},{"key":"454_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.es.01.110170.000245","volume":"1","author":"RC Lewontin","year":"1970","unstructured":"Lewontin, R. C. The units of selection. Annu. Rev. Ecol. Evol. Syst. 1, 1\u201318 https:\/\/doi.org\/10.1146\/annurev.es.01.110170.000245 (1970).","journal-title":"Annu. Rev. Ecol. Evol. Syst."},{"key":"454_CR32","doi-asserted-by":"crossref","unstructured":"Szathm\u00e1ry, E., Santos, M. & Fernando, C. Evolutionary potential and requirements for minimal protocells. In Prebiotic Chemistry (ed. Walde, P.) 167\u2013211 (Springer, 2005).","DOI":"10.1007\/tcc001"},{"key":"454_CR33","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nchem.1650","volume":"5","author":"K Adamala","year":"2013","unstructured":"Adamala, K. & Szostak, J. W. Competition between model protocells driven by an encapsulated catalyst. Nat. Chem. 5, 495\u2013501 https:\/\/doi.org\/10.1038\/nchem.1650 (2013).","journal-title":"Nat. Chem."},{"key":"454_CR34","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1126\/science.aag1582","volume":"354","author":"S Matsumura","year":"2016","unstructured":"Matsumura, S. et al. Transient compartmentalization of RNA replicators prevents extinction due to parasites. Science 354, 1293\u20131296 https:\/\/doi.org\/10.1126\/science.aag1582 (2016).","journal-title":"Science"},{"key":"454_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39175-0","volume":"14","author":"OA Saleh","year":"2023","unstructured":"Saleh, O. A., Wilken, S., Squires, T. M. & Liedl, T. Vacuole dynamics and popping-based motility in liquid droplets of DNA. Nat. Commun. 14, 3574 https:\/\/doi.org\/10.1038\/s41467-023-39175-0 (2023).","journal-title":"Nat. Commun."},{"key":"454_CR36","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1038\/s44286-024-00077-7","volume":"1","author":"NA Erkamp","year":"2024","unstructured":"Erkamp, N. A. et al. Biomolecular condensates with complex architectures via controlled nucleation. Nat. Chem. Eng. 1, 430\u2013439 https:\/\/doi.org\/10.1038\/s44286-024-00077-7 (2024).","journal-title":"Nat. Chem. Eng."},{"key":"454_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42344-w","volume":"14","author":"AM Bergmann","year":"2023","unstructured":"Bergmann, A. M. et al. Liquid spherical shells are a non-equilibrium steady state of active droplets. Nat. Commun. 14, 6552 https:\/\/doi.org\/10.1038\/s41467-023-42344-w (2023).","journal-title":"Nat. Commun."},{"key":"454_CR38","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1126\/science.1253920","volume":"345","author":"C Geary","year":"2014","unstructured":"Geary, C., Rothemund, P. W. K. & Andersen, E. S. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 345, 799\u2013804 https:\/\/doi.org\/10.1126\/science.1253920 (2014).","journal-title":"Science"},{"key":"454_CR39","doi-asserted-by":"publisher","first-page":"14410","DOI":"10.1021\/bi981371j","volume":"37","author":"C Wilson","year":"1998","unstructured":"Wilson, C., Nix, J. & Szostak, J. Functional requirements for specific ligand recognition by a biotin-binding RNA pseudoknot. Biochemistry 37, 14410\u201314419 https:\/\/doi.org\/10.1021\/bi981371j (1998).","journal-title":"Biochemistry"},{"key":"454_CR40","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41565-025-01879-3","volume":"20","author":"MP Tran","year":"2025","unstructured":"Tran, M. P. et al. Genetic encoding and expression of RNA origami cytoskeletons in synthetic cells. Nat. Nanotechnol. 20, 664\u2013671 https:\/\/doi.org\/10.1038\/s41565-025-01879-3 (2025).","journal-title":"Nat. Nanotechnol."},{"key":"454_CR41","doi-asserted-by":"publisher","first-page":"4890","DOI":"10.1039\/D3NR06423A","volume":"16","author":"N De Franceschi","year":"2024","unstructured":"De Franceschi, N., Hoogenberg, B., Katan, A. & Dekker, C. Engineering ssRNA tile filaments for (dis)assembly and membrane binding. Nanoscale 16, 4890\u20134899 https:\/\/doi.org\/10.1039\/D3NR06423A (2024).","journal-title":"Nanoscale"},{"key":"454_CR42","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.1021\/acsmacrolett.0c00709","volume":"9","author":"N Chen","year":"2020","unstructured":"Chen, N., Zhao, Z., Wang, Y. & Dimova, R. Resolving the mechanisms of soy glycinin self-coacervation and hollow-condensate formation. ACS Macro Lett. 9, 1844\u20131852 https:\/\/doi.org\/10.1021\/acsmacrolett.0c00709 (2020).","journal-title":"ACS Macro Lett."},{"key":"454_CR43","doi-asserted-by":"publisher","first-page":"7090","DOI":"10.1021\/jacs.3c00997","volume":"145","author":"W Liu","year":"2023","unstructured":"Liu, W., Lupfer, C., Samanta, A., Sarkar, A. & Walther, A. Switchable hydrophobic pockets in DNA protocells enhance chemical conversion. J. Am. Chem. Soc. 145, 7090\u20137094 https:\/\/doi.org\/10.1021\/jacs.3c00997 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"454_CR44","doi-asserted-by":"publisher","unstructured":"Myers, F. A. Random mutagenesis by PCR. In DNA Manipulation and Analysis (ed. Scarlett, G.) 81\u201386 https:\/\/doi.org\/10.1007\/978-1-0716-3004-4_7 (Humana, 2023).","DOI":"10.1007\/978-1-0716-3004-4_7"},{"key":"454_CR45","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1093\/nar\/gkh315","volume":"32","author":"C Neylon","year":"2004","unstructured":"Neylon, C. Chemical and biochemical strategies for the randomization of protein encoding DNA sequences: library construction methods for directed evolution. Nucleic Acids Res. 32, 1448\u20131459 https:\/\/doi.org\/10.1093\/nar\/gkh315 (2004).","journal-title":"Nucleic Acids Res."},{"key":"454_CR46","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1006\/jmbi.1996.0049","volume":"255","author":"M Zaccolo","year":"1996","unstructured":"Zaccolo, M., Williams, D. M., Brown, D. M. & Gherardi, E. An approach to random mutagenesis of DNA using mixtures of triphosphate derivatives of nucleoside analogues. J. Mol. Biol. 255, 589\u2013603 https:\/\/doi.org\/10.1006\/jmbi.1996.0049 (1996).","journal-title":"J. Mol. Biol."},{"key":"454_CR47","doi-asserted-by":"publisher","first-page":"7378","DOI":"10.1073\/pnas.81.23.7378","volume":"81","author":"WS El-Deiry","year":"1984","unstructured":"El-Deiry, W. S., Downey, K. M. & So, A. G. Molecular mechanisms of manganese mutagenesis. Proc. Natl Acad. Sci. USA 81, 7378\u20137382 (1984).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"454_CR48","doi-asserted-by":"publisher","first-page":"10815","DOI":"10.1038\/s41467-025-66290-x","volume":"16","author":"L Monari","year":"2025","unstructured":"Monari, L., Braun, I., Verstraeten, W., Poppleton, E. & G\u00f6pfrich, K. PyFuRNAce: an integrated design engine for RNA origami. Nat. Commun. 16, 10815 https:\/\/doi.org\/10.1038\/s41467-025-66290-x (2025).","journal-title":"Nat. Commun."},{"key":"454_CR49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63445-8","volume":"16","author":"M Xie","year":"2025","unstructured":"Xie, M., Chen, W., Vonk-de Roy, M. & Walther, A. Constructing synthetic nuclear architectures via transcriptional condensates in a DNA protonucleus. Nat. Commun. 16, 8254 https:\/\/doi.org\/10.1038\/s41467-025-63445-8 (2025).","journal-title":"Nat. Commun."},{"key":"454_CR50","doi-asserted-by":"publisher","first-page":"15633","DOI":"10.1073\/pnas.1304632110","volume":"110","author":"S Biffi","year":"2013","unstructured":"Biffi, S. et al. Phase behavior and critical activated dynamics of limited-valence DNA nanostars. Proc. Natl Acad. Sci. USA 110, 15633\u201315637 https:\/\/doi.org\/10.1073\/pnas.1304632110 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"454_CR51","doi-asserted-by":"publisher","first-page":"15650","DOI":"10.1073\/pnas.1922365117","volume":"117","author":"I Alshareedah","year":"2020","unstructured":"Alshareedah, I., Moosa, M. M., Raju, M., Potoyan, D. A. & Banerjee, P. R. Phase transition of RNA\u2013protein complexes into ordered hollow condensates. Proc. Natl Acad. Sci. USA 117, 15650\u201315658 https:\/\/doi.org\/10.1073\/pnas.1922365117 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"454_CR52","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.1038\/s41467-025-59100-x","volume":"16","author":"H Udono","year":"2025","unstructured":"Udono, H., Nomura, S.-i. M. & Takinoue, M. Remote-controlled mechanical and directional motions of photoswitchable DNA condensates. Nat. Commun. 16, 4479 https:\/\/doi.org\/10.1038\/s41467-025-59100-x (2025).","journal-title":"Nat. Commun."},{"key":"454_CR53","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1038\/s41563-025-02202-0","volume":"24","author":"QH Zhao","year":"2025","unstructured":"Zhao, Q. H., Qi, J. Y. & Deng, N. N. DNA photofluids show life-like motion. Nat. Mater. 24, 935\u2013944 https:\/\/doi.org\/10.1038\/s41563-025-02202-0 (2025).","journal-title":"Nat. Mater."},{"key":"454_CR54","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1146\/annurev-conmatphys-031115-011517","volume":"7","author":"CC Maass","year":"2016","unstructured":"Maass, C. C., Kr\u00fcger, C., Herminghaus, S. & Bahr, C. Swimming droplets. Annu. Rev. Condens. Matter Phys. 7, 171\u2013193 https:\/\/doi.org\/10.1146\/annurev-conmatphys-031115-011517 (2016).","journal-title":"Annu. Rev. Condens. Matter Phys."},{"key":"454_CR55","doi-asserted-by":"publisher","first-page":"5362","DOI":"10.1529\/biophysj.108.131250","volume":"95","author":"AB Goins","year":"2008","unstructured":"Goins, A. B., Sanabria, H. & Waxham, M. N. Macromolecular crowding and size effects on probe microviscosity. Biophys. J. 95, 5362\u20135373 https:\/\/doi.org\/10.1529\/biophysj.108.131250 (2008).","journal-title":"Biophys. J."},{"key":"454_CR56","doi-asserted-by":"publisher","first-page":"29344","DOI":"10.1021\/jacs.4c07555","volume":"146","author":"M Dizani","year":"2024","unstructured":"Dizani, M., Sorrentino, D., Agarwal, S., Stewart, J. M. & Franco, E. Protein recruitment to dynamic DNA\u2013RNA host condensates. J. Am. Chem. Soc. 146, 29344\u201329354 https:\/\/doi.org\/10.1021\/jacs.4c07555 (2024).","journal-title":"J. Am. Chem. Soc."},{"key":"454_CR57","doi-asserted-by":"publisher","first-page":"15477","DOI":"10.1021\/acsnano.3c12161","volume":"18","author":"H Udono","year":"2024","unstructured":"Udono, H. et al. Programmable computational RNA droplets assembled via kissing-loop interaction. ACS Nano 18, 15477\u201315486 https:\/\/doi.org\/10.1021\/acsnano.3c12161 (2024).","journal-title":"ACS Nano"},{"key":"454_CR58","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/s41557-022-00890-8","volume":"14","author":"JM Iglesias-Artola","year":"2022","unstructured":"Iglesias-Artola, J. M. et al. Charge-density reduction promotes ribozyme activity in RNA\u2013peptide coacervates via RNA fluidization and magnesium partitioning. Nat. Chem. 14, 407\u2013416 https:\/\/doi.org\/10.1038\/s41557-022-00890-8 (2022).","journal-title":"Nat. Chem."},{"key":"454_CR59","doi-asserted-by":"publisher","first-page":"e19002","DOI":"10.1002\/anie.202519002","volume":"65","author":"F Giessler","year":"2026","unstructured":"Giessler, F., Verstraeten, W., Abele, T., Maurer, S. J., Monari, L. & G\u00f6pfrich, K. Growth, dissolution and segregation of genetically encoded RNA droplets by ribozyme catalysis. Angew. Chem. Int. Ed. 65, e19002 https:\/\/doi.org\/10.1002\/anie.202519002 (2026).","journal-title":"Angew. Chem. Int. Ed."},{"key":"454_CR60","doi-asserted-by":"publisher","first-page":"e83543","DOI":"10.7554\/eLife.83543","volume":"12","author":"KK Le Vay","year":"2023","unstructured":"Le Vay, K. K., Salibi, E., Ghosh, B., Tang, T. D. & Mutschler, H. Ribozyme activity modulates the physical properties of RNA-peptide coacervates. eLife 12, e83543 https:\/\/doi.org\/10.7554\/eLife.83543 (2023).","journal-title":"eLife"},{"key":"454_CR61","doi-asserted-by":"publisher","unstructured":"Jaiswal, P., Haugerud, I. S. & Weber, C. A. Genetic encoding and mutagenesis of RNA droplet phenotypes. Zenodo https:\/\/doi.org\/10.5281\/zenodo.21979218 (2026).","DOI":"10.5281\/zenodo.21979218"}],"container-title":["Nature Chemical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44286-026-00454-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44286-026-00454-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44286-026-00454-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:05:14Z","timestamp":1792451114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44286-026-00454-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,7]]},"references-count":61,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["454"],"URL":"https:\/\/doi.org\/10.1038\/s44286-026-00454-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv-2025-5ffnn-v2","asserted-by":"object"}]},"ISSN":["2948-1198"],"issn-type":[{"value":"2948-1198","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,7]]},"assertion":[{"value":"28 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}