[{"article_processing_charge":"No","_id":"22959","day":"17","oa_version":"Published Version","fulldoi":"https://doi.org/10.1093/protein/gzag020","language":[{"iso":"eng"}],"doi":"10.1093/protein/gzag020","article_type":"review","type":"journal_article","has_accepted_license":"1","article_number":"gzag020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Protein engineering: Status report","external_id":{"pmid":["42466865"]},"publication_status":"published","publication_identifier":{"issn":["1741-0126"],"eissn":["1741-0134"]},"citation":{"ama":"Ai H, Arnold FH, Barrick D, et al. Protein engineering: Status report. <i>Protein Engineering, Design and Selection</i>. 2026;39. doi:<a href=\"https://doi.org/10.1093/protein/gzag020\">10.1093/protein/gzag020</a>","short":"H. Ai, F.H. Arnold, D. Barrick, H. Bayley, A.-L.R. Brownless, R.E. Campbell, R. Castells-Graells, P. Chaiyen, R.A. Chica, L.O. Chisholm, D. Christ, G.-C. Chu, M. Chungyoun, V.G.H. Eijsink, M.B. Elowitz, D.J. Fansher, R. Fasan, G. Foley, M.S. Frei, A. Gagsteiger, R. Gao, E.M.J. Gillam, J.J. Gray, L.F. Guerra, B. Höcker, Z. Jin, S.C.L. Kamerlin, N. Koga, R.E. Kontermann, B. Kuhlman, O.A. Langlois, D. Li, R.D. Lins, C.C. Liu, L. Liu, D. López Barreiro, P. Lu, S. Mehta, I. Miyazaki, M.M. Müller, S. Muyldermans, N. Nemoto, J. Nivala, J.K. Nuñez, I.J. Ornelas, J.N. Pelletier, A. Plückthun, O.T. Porth, K. Prakinee, Y. Qing, J. Reisenbauer, S. Schmidt, O. Seifert, M.G. Shapiro, R. Sharma, N. Singh, B.J. Smith, J.B. Spangler, R. Tatsumi-Koga, T. Terai, H. Terholsen, M. Tolhurst, K.W. Tripp, V.T. Trossmann, C.L. Tucker, O. Turak, J.A. Van Deventer, A. Várnai, I.F.T. Viana, A.M. Weeks, K.D. Wittrup, K.L.-J. Wong, C. Xi, T.O. Yeates, A.H.-W. Yeh, J. Zhang, T.S. Zhang, H. Zhao, F. Zheng, J. Zhu, S. Zinn, Protein Engineering, Design and Selection 39 (2026).","ieee":"H. Ai <i>et al.</i>, “Protein engineering: Status report,” <i>Protein Engineering, Design and Selection</i>, vol. 39. Oxford University Press, 2026.","mla":"Ai, Hui-wang, et al. “Protein Engineering: Status Report.” <i>Protein Engineering, Design and Selection</i>, vol. 39, gzag020, Oxford University Press, 2026, doi:<a href=\"https://doi.org/10.1093/protein/gzag020\">10.1093/protein/gzag020</a>.","apa":"Ai, H., Arnold, F. H., Barrick, D., Bayley, H., Brownless, A.-L. R., Campbell, R. E., … Zinn, S. (2026). Protein engineering: Status report. <i>Protein Engineering, Design and Selection</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/protein/gzag020\">https://doi.org/10.1093/protein/gzag020</a>","chicago":"Ai, Hui-wang, Frances H Arnold, Doug Barrick, Hagan Bayley, Alfie-Louise R Brownless, Robert E Campbell, Roger Castells-Graells, et al. “Protein Engineering: Status Report.” <i>Protein Engineering, Design and Selection</i>. Oxford University Press, 2026. <a href=\"https://doi.org/10.1093/protein/gzag020\">https://doi.org/10.1093/protein/gzag020</a>.","ista":"Ai H, Arnold FH, Barrick D, Bayley H, Brownless A-LR, Campbell RE, Castells-Graells R, Chaiyen P, Chica RA, Chisholm LO, Christ D, Chu G-C, Chungyoun M, Eijsink VGH, Elowitz MB, Fansher DJ, Fasan R, Foley G, Frei MS, Gagsteiger A, Gao R, Gillam EMJ, Gray JJ, Guerra LF, Höcker B, Jin Z, Kamerlin SCL, Koga N, Kontermann RE, Kuhlman B, Langlois OA, Li D, Lins RD, Liu CC, Liu L, López Barreiro D, Lu P, Mehta S, Miyazaki I, Müller MM, Muyldermans S, Nemoto N, Nivala J, Nuñez JK, Ornelas IJ, Pelletier JN, Plückthun A, Porth OT, Prakinee K, Qing Y, Reisenbauer J, Schmidt S, Seifert O, Shapiro MG, Sharma R, Singh N, Smith BJ, Spangler JB, Tatsumi-Koga R, Terai T, Terholsen H, Tolhurst M, Tripp KW, Trossmann VT, Tucker CL, Turak O, Van Deventer JA, Várnai A, Viana IFT, Weeks AM, Wittrup KD, Wong KL-J, Xi C, Yeates TO, Yeh AH-W, Zhang J, Zhang TS, Zhao H, Zheng F, Zhu J, Zinn S. 2026. Protein engineering: Status report. Protein Engineering, Design and Selection. 39, gzag020."},"pmid":1,"scopus_import":"1","OA_type":"hybrid","status":"public","ddc":["570"],"quality_controlled":"1","intvolume":"        39","volume":39,"year":"2026","publication":"Protein Engineering, Design and Selection","researchdata_availability":"no","publisher":"Oxford University Press","file_date_updated":"2026-10-01T09:24:22Z","oa":1,"author":[{"first_name":"Hui-wang","full_name":"Ai, Hui-wang","last_name":"Ai"},{"first_name":"Frances H","full_name":"Arnold, Frances H","last_name":"Arnold"},{"last_name":"Barrick","first_name":"Doug","full_name":"Barrick, Doug"},{"last_name":"Bayley","first_name":"Hagan","full_name":"Bayley, Hagan"},{"last_name":"Brownless","full_name":"Brownless, Alfie-Louise R","first_name":"Alfie-Louise R"},{"last_name":"Campbell","first_name":"Robert E","full_name":"Campbell, Robert E"},{"full_name":"Castells-Graells, Roger","first_name":"Roger","last_name":"Castells-Graells"},{"first_name":"Pimchai","full_name":"Chaiyen, Pimchai","last_name":"Chaiyen"},{"full_name":"Chica, Roberto A","first_name":"Roberto A","last_name":"Chica"},{"last_name":"Chisholm","first_name":"Lauren O","full_name":"Chisholm, Lauren O"},{"full_name":"Christ, Daniel","first_name":"Daniel","last_name":"Christ"},{"last_name":"Chu","first_name":"Guo-Chao","full_name":"Chu, Guo-Chao"},{"last_name":"Chungyoun","first_name":"Michael","full_name":"Chungyoun, Michael"},{"last_name":"Eijsink","first_name":"Vincent G H","full_name":"Eijsink, Vincent G H"},{"full_name":"Elowitz, Michael B","first_name":"Michael B","last_name":"Elowitz"},{"first_name":"Douglas J","full_name":"Fansher, Douglas J","last_name":"Fansher"},{"full_name":"Fasan, Rudi","first_name":"Rudi","last_name":"Fasan"},{"first_name":"Gabriel","full_name":"Foley, Gabriel","last_name":"Foley"},{"last_name":"Frei","full_name":"Frei, Michelle S","first_name":"Michelle S"},{"first_name":"Andreas","full_name":"Gagsteiger, Andreas","last_name":"Gagsteiger"},{"last_name":"Gao","full_name":"Gao, Ruiyan","first_name":"Ruiyan"},{"full_name":"Gillam, Elizabeth M J","first_name":"Elizabeth M J","last_name":"Gillam"},{"first_name":"Jeffrey J","full_name":"Gray, Jeffrey J","last_name":"Gray"},{"last_name":"Guerra","first_name":"Luis F","full_name":"Guerra, Luis F"},{"full_name":"Höcker, Birte","first_name":"Birte","last_name":"Höcker"},{"full_name":"Jin, Zhiyang","first_name":"Zhiyang","last_name":"Jin"},{"last_name":"Kamerlin","full_name":"Kamerlin, Shina Caroline Lynn","first_name":"Shina Caroline Lynn"},{"last_name":"Koga","full_name":"Koga, Nobuyasu","first_name":"Nobuyasu"},{"first_name":"Roland E","full_name":"Kontermann, Roland E","last_name":"Kontermann"},{"first_name":"Brian","full_name":"Kuhlman, Brian","last_name":"Kuhlman"},{"last_name":"Langlois","full_name":"Langlois, Olivia A","first_name":"Olivia A"},{"full_name":"Li, Dongyang","first_name":"Dongyang","last_name":"Li"},{"first_name":"Roberto D","full_name":"Lins, Roberto D","last_name":"Lins"},{"last_name":"Liu","full_name":"Liu, Chang C","first_name":"Chang C"},{"last_name":"Liu","first_name":"Lei","full_name":"Liu, Lei"},{"full_name":"López Barreiro, Diego","first_name":"Diego","last_name":"López Barreiro"},{"last_name":"Lu","full_name":"Lu, Peilong","first_name":"Peilong"},{"last_name":"Mehta","full_name":"Mehta, Sohum","first_name":"Sohum"},{"full_name":"Miyazaki, Ikumi","first_name":"Ikumi","last_name":"Miyazaki"},{"last_name":"Müller","full_name":"Müller, Manuel M","first_name":"Manuel M"},{"full_name":"Muyldermans, Serge","first_name":"Serge","last_name":"Muyldermans"},{"last_name":"Nemoto","first_name":"Naoto","full_name":"Nemoto, Naoto"},{"last_name":"Nivala","first_name":"Jeff","full_name":"Nivala, Jeff"},{"first_name":"James K","full_name":"Nuñez, James K","last_name":"Nuñez"},{"full_name":"Ornelas, Izaiah J","first_name":"Izaiah J","last_name":"Ornelas"},{"full_name":"Pelletier, Joelle N","first_name":"Joelle N","last_name":"Pelletier"},{"last_name":"Plückthun","first_name":"Andreas","full_name":"Plückthun, Andreas"},{"first_name":"Owen T","full_name":"Porth, Owen T","last_name":"Porth"},{"first_name":"Kridsadakorn","full_name":"Prakinee, Kridsadakorn","last_name":"Prakinee"},{"last_name":"Qing","first_name":"Yujia","full_name":"Qing, Yujia"},{"id":"51d862e9-36ee-11f0-86d3-8534c85a5496","first_name":"Julia","full_name":"Reisenbauer, Julia","last_name":"Reisenbauer"},{"full_name":"Schmidt, Sandy","first_name":"Sandy","last_name":"Schmidt"},{"last_name":"Seifert","first_name":"Oliver","full_name":"Seifert, Oliver"},{"full_name":"Shapiro, Mikhail G","first_name":"Mikhail G","last_name":"Shapiro"},{"last_name":"Sharma","first_name":"Rachna","full_name":"Sharma, Rachna"},{"last_name":"Singh","first_name":"Nilmani","full_name":"Singh, Nilmani"},{"full_name":"Smith, Benjamin J","first_name":"Benjamin J","last_name":"Smith"},{"last_name":"Spangler","first_name":"Jamie B","full_name":"Spangler, Jamie B"},{"first_name":"Rie","full_name":"Tatsumi-Koga, Rie","last_name":"Tatsumi-Koga"},{"full_name":"Terai, Takuya","first_name":"Takuya","last_name":"Terai"},{"last_name":"Terholsen","full_name":"Terholsen, Henrik","first_name":"Henrik"},{"first_name":"Mattias","full_name":"Tolhurst, Mattias","last_name":"Tolhurst"},{"first_name":"Katherine W","full_name":"Tripp, Katherine W","last_name":"Tripp"},{"last_name":"Trossmann","full_name":"Trossmann, Vanessa Tanja","first_name":"Vanessa Tanja"},{"first_name":"Chandra L","full_name":"Tucker, Chandra L","last_name":"Tucker"},{"last_name":"Turak","first_name":"Onur","full_name":"Turak, Onur"},{"first_name":"James A","full_name":"Van Deventer, James A","last_name":"Van Deventer"},{"last_name":"Várnai","first_name":"Anikó","full_name":"Várnai, Anikó"},{"full_name":"Viana, Isabelle F T","first_name":"Isabelle F T","last_name":"Viana"},{"last_name":"Weeks","full_name":"Weeks, Amy M","first_name":"Amy M"},{"last_name":"Wittrup","full_name":"Wittrup, K Dane","first_name":"K Dane"},{"first_name":"Kingsley L-J","full_name":"Wong, Kingsley L-J","last_name":"Wong"},{"first_name":"Chenggang","full_name":"Xi, Chenggang","last_name":"Xi"},{"last_name":"Yeates","full_name":"Yeates, Todd O","first_name":"Todd O"},{"first_name":"Andy Hsien-Wei","full_name":"Yeh, Andy Hsien-Wei","last_name":"Yeh"},{"full_name":"Zhang, Jin","first_name":"Jin","last_name":"Zhang"},{"last_name":"Zhang","full_name":"Zhang, Tiger S","first_name":"Tiger S"},{"last_name":"Zhao","full_name":"Zhao, Huimin","first_name":"Huimin"},{"last_name":"Zheng","first_name":"Fang","full_name":"Zheng, Fang"},{"full_name":"Zhu, Jingyi","first_name":"Jingyi","last_name":"Zhu"},{"first_name":"Sacha","full_name":"Zinn, Sacha","last_name":"Zinn"}],"abstract":[{"text":"With this status report, we aim to provide a timely snapshot of the protein engineering field as a broad and rapidly advancing discipline that integrates computational, molecular biology, structure-guided, evolutionary, and synthetic approaches to create new and improved proteins with tailored structures and useful functions. The report is organized into eight thematic areas spanning core methodologies and major application domains, including enzymes, therapeutics, detection, synthetic biology, and materials. Contributions from experts across these areas highlight both the historical foundations and recent advances in their respective fields, with particular emphasis on the growing influence of machine learning and artificial intelligence-based methods. Emerging from this broad overview is a central message: protein engineering appears to be entering a golden age, defined by a rapidly accelerating pace of progress, even as significant challenges in design, screening, and real-world application remain. Looking ahead, the continued integration of computational and experimental strategies is poised to further accelerate the impact of protein engineering across an expanding range of economically and societally important sectors, from therapeutics and molecular imaging to diagnostics, plastic recycling, and industrial chemistry.","lang":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"dataavailabilitystatement":"No new data were generated or analysed in support of this research.","date_published":"2026-07-17T00:00:00Z","license":"https://creativecommons.org/licenses/by/4.0/","month":"07","OA_place":"publisher","supplementarymaterial":"no","file":[{"relation":"main_file","content_type":"application/pdf","file_size":12603911,"file_id":"23019","creator":"dernst","access_level":"open_access","date_updated":"2026-10-01T09:24:22Z","checksum":"4015ecfe11b3b0cac757d5bdd10d3c1d","date_created":"2026-10-01T09:24:22Z","success":1,"file_name":"2026_ProteinEngineeringDesignSelection_Ai.pdf"}],"das_tickbox":"1","date_updated":"2026-10-01T09:29:15Z","department":[{"_id":"JuRe"}],"date_created":"2026-09-17T11:06:36Z","acknowledgement":"Research in the lab of H.A. is supported by the National Institutes of Health (R01EB033172, R01EB035430, and R01AG077773).\r\n\r\nResearch in the lab of F.H.A. is supported by the US Army Research Office cooperative agreement for the Institute for Collaborative Biotechnologies (W911NF-19-2-0026) and the US Department of Energy, Office of Science, Office of Basic Energy Sciences (DE-SC0021141). This report was prepared as an account of work sponsored by an agency of the US Government. Neither the US Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the US Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily state or reflect those of the US Government or any agency thereof.\r\n\r\nResearch in the lab of D.B. has been supported by National Institutes of Health (NIH) (R35-GM158123-01 and R01-GM068462).\r\n\r\nResearch in the lab of H.B. is supported by grants from the Bill & Melinda Gates Foundation and Oxford Nanopore Technologies.\r\n\r\nResearch in the lab of R.E.C. is supported by grants from the Japan Society for the Promotion of Science (JSPS) (23K26794, 24H00489, and 24H02267), Japan Science and Technology Agency (JST) (JPMJCR25T3), the Mitsubishi Foundation, and the NIH (U01NS123658).\r\n\r\nResearch in the lab of P.C. is supported by grants from the Vidyasirimedhi Institute of Science and Technology (VISTEC), NSRF via the Program Management Unit for Human Resources & Institutional Development (PMU-B) Research and Innovation grant number B05F640089, and KasikornBank Public Company Limited.\r\n\r\nResearch in the lab of R.A.C. is supported by grants from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2021-03484, RGPAS-2021-00017, and ALLRP-597074-24), the Human Frontier Science Program (RGP0004/2022) and the Canada Foundation for Innovation (26503 and 42695). B.J.S. was supported by an NSERC Canada Graduate Research Scholarship.\r\n\r\nResearch in the lab of V.G.H.E. is supported by grants from the European Research Council, ERC (grant number 856446, CUBE), the Novo Nordisk Foundation (Emerging Investigator grant to A.V.; grant number 0061165) and the Research Council of Norway (grant numbers 309558, Centre for Industrial Biotechnology, SFI-IB, and 257622, Bio4Fuels).\r\n\r\nThis project in the lab of R.F. was supported by Robert A. Welch Foundation (AT-0051-20221212), and the Cancer Prevention and Research Institute of Texas (grant RR230018).\r\n\r\nResearch in the lab of M.S.F. is supported by ETH Zurich and the Swiss National Science Foundation (SNSF) under grant number CR00I5-235927.\r\n\r\nThis project in the lab of J.J.G is supported by the NIH (R35 GM141881) and a National Science Foundation (NSF) Graduate Research Fellowship Program to M.C.\r\n\r\nRelated research in the lab of B.H. is supported by the German Research Foundation (DFG) Project Number 391977956—SFB 1357 Microplastics, subproject C03 and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No 951375 (ERC Synergy—ArtMotor).\r\n\r\nRelated work in the lab of S.C.L.K. is supported by the NSF under Grant No. 2414074. S.C.L.K. is the Georgia Research Alliance—Vasser Wooley Chair of Molecular Design at Georgia Tech.\r\n\r\nResearch in the lab of N.K. is supported by grants from the JSPS (24H02261).\r\n\r\nThis project in the lab of B.K. was supported by the NIH (R35 GM131923).\r\n\r\nResearch in the lab of R.E.K. on bispecific antibodies is supported by a grant from the Baden-Württemberg Stiftung and various industry collaborations. Past research was funded by the Deutsche Krebshilfe, the BMBF, and the Deutsche Forschungsgemeinschaft.\r\n\r\nResearch in the lab of R.D.L. (Protein Engineering and Structural Genomics group) is supported by grants from Brazilian National Research Council—CNPq (303833/2022-0, 307370/2025-9), the Oswaldo Cruz Fondation—Fiocruz (VPPIS-004-FIO-22, IAM-005-FIO-22, VPPCB-002-FIO25), and the Brazilian National Supercomputing Center—LNCC.\r\n\r\nChemical protein synthesis research in the lab of L.L. is supported by NSFC (22137005, 22227810, T2488301) and New Cornerstone Science Foundation.\r\n\r\nResearch in the lab of M.M.M. is supported by a Wellcome Trust/Royal Society Sir Henry Dale Fellowship (202250/Z/16/Z); the Biotechnology and Biological Sciences Research Council (BB/W015730/1) and a UKRI Postdoc Guarantee Fellowship (Horizon Europe Guarantee via EPSRC EP/Z000823/1 to L.F.G).\r\n\r\nResearch in the lab of F.Z. is partially supported by the Natural Science Foundation of Shaanxi Province (2025SF-YBXM-421).\r\n\r\nResearch in the lab of J.K.N. is supported by the NIH (R35GM155044), Biohub, San Francisco, the Pew Charitable Trusts, The Vallee Foundation, The Shurl and Kay Curci Foundation, the Bakar Fellows Program, and a Sloan Research Fellowship. I.J.O. acknowledges support from a Gilliam Fellowship from the Howard Hughes Medical Institute.\r\n\r\nResearch in the lab of J.N.P. is supported by the Natural Science and Engineering Research Council of Canada (RGPIN-N-2018-04686) and the Canada Research Chair in Engineering of Applied Proteins (CRC-2020-00171). D.J.F. is supported by a fellowship from the Fonds de recherche du Québec.\r\n\r\nResearch in the lab of A.P. has been supported predominantly by grants from the SNSF, the European Union, the European Research Council, as well as by pre- and postdoctoral fellowships to the co-workers.\r\n\r\nResearch in the lab of Y.Q. is supported by a Horizon Europe Guarantee ERC Starting Grant (EP/Z000351/1) and a Biotechnology and Biological Sciences Research Council Research Grant (BB/W00349X/1).\r\n\r\nJ.C.R. acknowledges partial support from the SNSF Postdoc.Mobility (P500PN_214290). The author thanks Chenghao Liu and Jason Yang for fruitful discussions.\r\n\r\nResearch in the lab of S.S. is supported by a NWO-VIDI grant from the Netherlands Organization for Scientific Research (NWO, VI.Vidi.213.025) and the European Research Council, ERC (grant agreement number 101075934, ReCNNSTRCT).\r\n\r\nResearch in the lab of J.B.S. is supported by a Helmsley Charitable Trust grant and a Swim Across America grant.\r\n\r\nThis project in the lab of C.L.T. was supported by a grant from the National Institute of General Medical Sciences of the NIH (R35GM136367).\r\n\r\nResearch on ncAAs in the lab of J.A.V. is supported by a grant from the National Institute of General Medical Sciences of the NIH (R35GM133471) and a grant from the NSF (2339201). The content is solely the responsibility of the author and does not necessarily represent the official views of the NIH or the NSF.\r\n\r\nResearch in the lab of A.M.W is supported by an NIH Director’s New Innovator Award (DP2GM149548), a David and Lucille Packard Fellowship for Science and Engineering (2021-73007), an Ono Pharma Foundation Breakthrough Science Initiative Award (149802896), and the University of Wisconsin—Madison Department of Biochemistry.\r\n\r\nProjects in the lab of A.H-W.Y. are supported by NIH/NIBIB R00EB031913, UCSC startup/Innovation Catalyst Grant, and Chan Zuckerberg Initiative (2024-337820).\r\n\r\nResearch in the lab of J.Zhang is supported by NIH grants R35 CA197622, R01 DK073368, R01 DE030497, R01 HL162302, R01 CA262815, and RF1 MH126707.\r\n\r\nResearch in the lab of H. Z. is supported by the DOE Center for Advanced Bioenergy and Bioproducts Innovation (U.S. Department of Energy, Office of Science, Biological and Environmental Research Program under Award Number DE-SC0018420), National Science Foundation (NSF) (DBI-2400058, OISE-2435374, IIS-2435755, and CHE-2505932), and National Institutes of Health (NIH) (AI144967). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the DOE, NSF or NIH.\r\n\r\nThe authors are grateful to the anonymous peer reviewers and to Anna Devor for inspiration and guidance for preparing this manuscript."},{"type":"journal_article","article_type":"original","isi":1,"day":"01","_id":"10363","oa_version":"Published Version","fulldoi":"https://doi.org/10.1093/protein/gzab025","language":[{"iso":"eng"}],"doi":"10.1093/protein/gzab025","article_processing_charge":"No","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/protein/gzab025"}],"citation":{"chicago":"Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R. Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>. Oxford University Press, 2021. <a href=\"https://doi.org/10.1093/protein/gzab025\">https://doi.org/10.1093/protein/gzab025</a>.","ista":"Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 34, gzab025.","short":"J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver, Protein Engineering, Design and Selection 34 (2021).","ama":"Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin fusion protein to treat hypoxia. <i>Protein Engineering, Design and Selection</i>. 2021;34. doi:<a href=\"https://doi.org/10.1093/protein/gzab025\">10.1093/protein/gzab025</a>","mla":"Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” <i>Protein Engineering, Design and Selection</i>, vol. 34, gzab025, Oxford University Press, 2021, doi:<a href=\"https://doi.org/10.1093/protein/gzab025\">10.1093/protein/gzab025</a>.","ieee":"J. Lee <i>et al.</i>, “Rational engineering of an erythropoietin fusion protein to treat hypoxia,” <i>Protein Engineering, Design and Selection</i>, vol. 34. Oxford University Press, 2021.","apa":"Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C., &#38; Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein to treat hypoxia. <i>Protein Engineering, Design and Selection</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/protein/gzab025\">https://doi.org/10.1093/protein/gzab025</a>"},"title":"Rational engineering of an erythropoietin fusion protein to treat hypoxia","external_id":{"pmid":["34725710"],"isi":["000746596900001"]},"publication_status":"published","publication_identifier":{"eissn":["1741-0134"],"issn":["1741-0126"]},"article_number":"gzab025","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"author":[{"first_name":"Jungmin","full_name":"Lee, Jungmin","last_name":"Lee"},{"first_name":"Andyna","full_name":"Vernet, Andyna","last_name":"Vernet"},{"full_name":"Gruber, Nathalie","id":"2C9C8316-AA17-11E9-B5C2-8BC2E5697425","first_name":"Nathalie","last_name":"Gruber"},{"last_name":"Kready","full_name":"Kready, Kasia M.","first_name":"Kasia M."},{"first_name":"Devin R.","full_name":"Burrill, Devin R.","last_name":"Burrill"},{"first_name":"Jeffrey C.","full_name":"Way, Jeffrey C.","last_name":"Way"},{"last_name":"Silver","first_name":"Pamela A.","full_name":"Silver, Pamela A."}],"abstract":[{"text":"Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.","lang":"eng"}],"publisher":"Oxford University Press","year":"2021","volume":34,"publication":"Protein Engineering, Design and Selection","pmid":1,"scopus_import":"1","OA_type":"free access","quality_controlled":"1","status":"public","ddc":["570"],"intvolume":"        34","department":[{"_id":"CaGu"}],"acknowledgement":"This work was supported by funds from the Wyss Institute for Biologically Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475; Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported by the Harvard Medical School Department of Systems Biology. J.C.W. was further supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V., D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant Number W911NF-17-2-0092. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein. We sincerely thank Amanda Graveline and the Wyss Institute at Harvard for their scientific support.","date_created":"2021-11-28T23:01:28Z","date_updated":"2026-07-28T12:27:59Z","month":"11","OA_place":"publisher","date_published":"2021-11-01T00:00:00Z"}]