{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:25:04Z","timestamp":1793348704154,"version":"4.5.0"},"posted":{"date-parts":[[2025,7,6]]},"group-title":"Synthetic Biology","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Despite breakthroughs in protein design enabled by artificial intelligence, reliably designing functional antibodies from scratch has remained an elusive challenge. Recent works show promise but still require large-scale experimental screening of thousands to millions of designs to reliably identify hits. In this work, we introduce Chai-2, a multimodal generative model that achieves a 16% hit rate in fully\n                  <jats:italic>de novo<\/jats:italic>\n                  antibody design, representing an over 100-fold improvement compared to previous computational methods. We prompt Chai-2 to design\n                  <jats:italic>\u2264<\/jats:italic>\n                  20 antibodies or nanobodies to 52 diverse targets, completing the workflow from AI design to wet-lab validation in under two weeks. Crucially, none of these targets have a preexisting antibody or nanobody binder in the Protein Data Bank. Remarkably, in just a single round of experimental testing, we find at least one successful hit for 50% of targets, often with strong affinities and favorable drug-like profiles. Beyond antibody design, Chai-2 achieves a 68% wet-lab success rate in miniprotein design \u2013 routinely yielding picomolar binders. The high success rate of Chai-2 enables rapid experimental validation and characterization of novel antibodies in under two weeks, paving the way toward a new era of rapid and precise atomic-level molecular engineering.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:caption>\n                      <jats:p>\n                        <jats:italic>52 antigens targeted by Chai-2. Blue boxes indicate targets with at least one successful binder out of \u226420 assayed designs, representing 50% of the tested targets<\/jats:italic>\n                        .\n                      <\/jats:p>\n                      <jats:p>\n                        <jats:bold>Date:<\/jats:bold>\n                        June 30, 2025\n                      <\/jats:p>\n                    <\/jats:caption>\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"663018v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.07.05.663018","type":"posted-content","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:45:14Z","timestamp":1751849114000},"source":"Crossref","is-referenced-by-count":49,"title":["Zero-shot antibody design in a 24-well plate"],"prefix":"10.64898","author":[{"name":"Chai Discovery Team","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Boitreaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Dent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny","family":"Geisz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"McPartlon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuoran","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Rogozhnikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Rollins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Wollenhaupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025070905100761000_2025.07.05.663018v1.1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403509101"},{"issue":"3","key":"2025070905100761000_2025.07.05.663018v1.2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3390\/antib8030044","article-title":"Phage display libraries for antibody therapeutic discovery and development","volume":"8","year":"2019","journal-title":"Antibodies"},{"key":"2025070905100761000_2025.07.05.663018v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01582-x"},{"key":"2025070905100761000_2025.07.05.663018v1.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028766"},{"key":"2025070905100761000_2025.07.05.663018v1.5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02030"},{"key":"2025070905100761000_2025.07.05.663018v1.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah4043"},{"key":"2025070905100761000_2025.07.05.663018v1.7","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2004.13167"},{"key":"2025070905100761000_2025.07.05.663018v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-021-00348-5"},{"key":"2025070905100761000_2025.07.05.663018v1.9","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAB1061"},{"key":"2025070905100761000_2025.07.05.663018v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/sci-ence.adl2528"},{"key":"2025070905100761000_2025.07.05.663018v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-024-07487-W"},{"key":"2025070905100761000_2025.07.05.663018v1.12","unstructured":"Chai Discovery team , Jacques Boitreaud , Jack Dent , Matthew McPartlon , Joshua Meier , Vinicius Reis , Alex Rogozhonikov , and Kevin Wu . 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