{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:05:33Z","timestamp":1790017533418,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Synthetic Biology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["P30CA275774"],"award-info":[{"award-number":["P30CA275774"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32EB019944"],"award-info":[{"award-number":["T32EB019944"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"U.S. National Science Foundation","award":["2127436"],"award-info":[{"award-number":["2127436"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Biological processes are often regulated through reactions involving supramolecular protein complexes organized with nanoscale precision, such as the apoptosome that activates procaspase-9 through defined stoichiometry to induce apoptosis. Here we report designer CASCAD (\n                  <jats:underline>C<\/jats:underline>\n                  ARD\n                  <jats:underline>A<\/jats:underline>\n                  ssembly on\n                  <jats:underline>SCA<\/jats:underline>\n                  ffold\n                  <jats:underline>D<\/jats:underline>\n                  NA), a self-assembled DNA nanoplatform that spatially organizes caspase recruitment domains (CARDs), exhibiting catalytic intracellular caspase-9 activation. By functioning like a natural apoptosome, CASCAD enhances caspase-9 oligomerization and promotes valency-dependent enzymatic activation. Further, after incorporating targeting aptamers and membrane-interacting peptides for cellular uptake and cytosolic delivery, CASCAD has successfully reconstituted apoptosome function and downstream apoptotic signaling in\n                  <jats:italic>in-vitro<\/jats:italic>\n                  2D and 3D cultures. Our molecular design paradigm establishes CASCAD as versatile and programmable DNA nanomaterial for reconstructing signaling pathways driven by diverse supramolecular complexes, including inflammasomes and myddosomes, providing a general chemical framework for engineering cellular signaling and directing cellular function and fate.\n                <\/jats:p>","DOI":"10.64898\/2026.09.15.751908","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:25:23Z","timestamp":1789673123000},"source":"Crossref","is-referenced-by-count":0,"title":["Programmable DNA Assemblies Reconstitute Supramolecular Protein Function"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3063-4408","authenticated-orcid":false,"given":"Dhanush","family":"Gandavadi","sequence":"first","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-8138","authenticated-orcid":false,"given":"Abhisek","family":"Dwivedy","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Holonyak Micro & Nanotechnology Lab, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8780-5783","authenticated-orcid":false,"given":"Revathi","family":"Manoharaan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1708-4082","authenticated-orcid":false,"given":"Seongmin","family":"Im","sequence":"additional","affiliation":[{"name":"Holonyak Micro & Nanotechnology Lab, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Department of Electrical and Computer Engineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9735-8062","authenticated-orcid":false,"given":"Saurabh","family":"Umrao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Holonyak Micro & Nanotechnology Lab, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9594-7737","authenticated-orcid":false,"given":"Chau Nguyen Minh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"VinUni-Illinois Smart Health Center, VinUniversity, Hanoi, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kadmos","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0154-3483","authenticated-orcid":false,"given":"Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Holonyak Micro & Nanotechnology Lab, the Grainger College of Engineering, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA"},{"name":"Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, 61801, USA"},{"name":"Carl R. 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