Matthew C. Watson, Kunal J. Rambhia, Meghan J. Seltzer, Sarah R. Carter, Rebecca L. Moritz, Aurelia Attal-Juncqua, James Diggans, John Dileo
{"title":"Toward a safer and more secure US bioeconomy","authors":"Matthew C. Watson, Kunal J. Rambhia, Meghan J. Seltzer, Sarah R. Carter, Rebecca L. Moritz, Aurelia Attal-Juncqua, James Diggans, John Dileo","doi":"10.1038/s41587-024-02519-2","DOIUrl":"10.1038/s41587-024-02519-2","url":null,"abstract":"To enhance the safety and security of the US bioeconomy, a new public–private partnership should be established to facilitate information sharing and threat analysis among industry, government and academia, and to develop and deploy safeguards.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"23-25"},"PeriodicalIF":33.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The devolution of biosimilars regulations","authors":"Erik Doevendans, Peter van Meer, Huub Schellekens","doi":"10.1038/s41587-024-02497-5","DOIUrl":"10.1038/s41587-024-02497-5","url":null,"abstract":"After two decades of experience with biosimilars, physicochemical and in vitro biological comparison with their reference products appear sufficient to guarantee clinical safety and efficacy. Hence, the regulation of biosimilars has become redundant, and biopharmaceuticals should now be regulated through the generic pathway available for small molecules.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"19-22"},"PeriodicalIF":33.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haotian Du, Jingjia Liu, Kevin M. Jude, Xinbo Yang, Ying Li, Braxton Bell, Hongli Yang, Audrey Kassardjian, Wyatt Blackson, Ali Mobedi, Udit Parekh, R. Andres Parra Sperberg, Jean-Philippe Julien, Elizabeth D. Mellins, K. Christopher Garcia, Po-Ssu Huang
{"title":"A general system for targeting MHC class II–antigen complex via a single adaptable loop","authors":"Haotian Du, Jingjia Liu, Kevin M. Jude, Xinbo Yang, Ying Li, Braxton Bell, Hongli Yang, Audrey Kassardjian, Wyatt Blackson, Ali Mobedi, Udit Parekh, R. Andres Parra Sperberg, Jean-Philippe Julien, Elizabeth D. Mellins, K. Christopher Garcia, Po-Ssu Huang","doi":"10.1038/s41587-024-02466-y","DOIUrl":"https://doi.org/10.1038/s41587-024-02466-y","url":null,"abstract":"<p>Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4<sup>+</sup> T cells and antigen-presenting cells. Targeting peptide–MHCII with T cell antigen receptors (TCRs) and TCR-like antibodies has shown promise for autoimmune diseases and microbiome tolerance. To develop a general targeting approach, we introduce targeted recognition of antigen–MHC complex reporter for MHCII (TRACeR-II) for the rapid development of peptide-specific MHCII binders. TRACeR-II binders have a small helical bundle scaffold and use a single loop to recognize peptide–MHCII, which offers versatility and enables structural modeling of the interactions to target MHCII antigens. We demonstrate rapid generation of TRACeR-II binders to multiple molecules with affinities in the low-nanomolar to low-micromolar range, comparable to best-in-class TCRs and antibodies. Through computational protein design, we created specific binding sequences in silico from only the sequence of a severe acute respiratory syndrome coronavirus 2 peptide. TRACeR-II provides a straightforward approach to target antigen–MHCII without relying on combinatorial selection on complementarity-determining region loops.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"352 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biopharma deals get smaller and earlier","authors":"Melanie Senior","doi":"10.1038/s41587-024-02506-7","DOIUrl":"10.1038/s41587-024-02506-7","url":null,"abstract":"Merger and acquisition activity is at a seven-year low in 2024 as buyers digest prior deals and US election jitters delayed further spending. Expect a pick-up in 2025.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"11-18"},"PeriodicalIF":33.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pallavi A. Balivada, Stephanie A. Gaglione, Michael E. Birnbaum
{"title":"A synthetic scaffold to target peptide–MHC complexes","authors":"Pallavi A. Balivada, Stephanie A. Gaglione, Michael E. Birnbaum","doi":"10.1038/s41587-024-02513-8","DOIUrl":"https://doi.org/10.1038/s41587-024-02513-8","url":null,"abstract":"A method for designing high-affinity, specific binders to peptide–MHC complexes may improve the next generation of antigen-specific T cell-based therapeutics.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"62 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haotian Du, Leena Mallik, Daniel Hwang, Yi Sun, Chengzi Kaku, Daniel Hoces, Shirley M. Sun, Reem Ghinnagow, Stephen D. Carro, Hoang Anh T. Phan, Sagar Gupta, Wyatt Blackson, Hyejin Lee, Christian A. Choe, Devin Dersh, Jingjia Liu, Braxton Bell, Hongli Yang, Georgia F. Papadaki, Michael C. Young, Emily Zhou, Gina El Nesr, Kimia Dasteh Goli, Laurence C. Eisenlohr, Andy J. Minn, Rogelio A. Hernandez-Lopez, Joseph G. Jardine, Nikolaos G. Sgourakis, Po-Ssu Huang
{"title":"Targeting peptide antigens using a multiallelic MHC I-binding system","authors":"Haotian Du, Leena Mallik, Daniel Hwang, Yi Sun, Chengzi Kaku, Daniel Hoces, Shirley M. Sun, Reem Ghinnagow, Stephen D. Carro, Hoang Anh T. Phan, Sagar Gupta, Wyatt Blackson, Hyejin Lee, Christian A. Choe, Devin Dersh, Jingjia Liu, Braxton Bell, Hongli Yang, Georgia F. Papadaki, Michael C. Young, Emily Zhou, Gina El Nesr, Kimia Dasteh Goli, Laurence C. Eisenlohr, Andy J. Minn, Rogelio A. Hernandez-Lopez, Joseph G. Jardine, Nikolaos G. Sgourakis, Po-Ssu Huang","doi":"10.1038/s41587-024-02505-8","DOIUrl":"https://doi.org/10.1038/s41587-024-02505-8","url":null,"abstract":"<p>Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen–MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR–MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions. We demonstrate rapid screening of TRACeR-I against a panel of disease-relevant HLAs with peptides derived from human viruses (human immunodeficiency virus, Epstein–Barr virus and severe acute respiratory syndrome coronavirus 2), and oncoproteins (Kirsten rat sarcoma virus, paired-like homeobox 2b and New York esophageal squamous cell carcinoma 1). TRACeR-based bispecific T cell engagers and chimeric antigen receptor T cells exhibit on-target killing of tumor cells with high efficacy in the low nanomolar range. Our platform empowers the development of broadly applicable MHC I-targeting molecules for research, diagnostic and therapeutic applications.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"15 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BioNTech boosts oncology pipeline with China buy","authors":"","doi":"10.1038/s41587-024-02518-3","DOIUrl":"10.1038/s41587-024-02518-3","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1761-1761"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keqiang Xie, Jakob Starzyk, Ishita Majumdar, Jiao Wang, Katerina Rincones, Thao Tran, Danna Lee, Sarah Niemi, John Famiglietti, Bernhard Suter, Richard Shan, Hao Wu
{"title":"Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration","authors":"Keqiang Xie, Jakob Starzyk, Ishita Majumdar, Jiao Wang, Katerina Rincones, Thao Tran, Danna Lee, Sarah Niemi, John Famiglietti, Bernhard Suter, Richard Shan, Hao Wu","doi":"10.1038/s41587-024-02504-9","DOIUrl":"https://doi.org/10.1038/s41587-024-02504-9","url":null,"abstract":"<p>The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture. In this study, we developed a non-viral genome writing catalyst (GATALYST) system that allows production of circular single-stranded DNAs (cssDNAs) up to approximately 20 kilobases as donor templates for highly efficient precision transgene integration. cssDNA donors enable knock-in efficiency of up to 70% in induced pluripotent stem cells (iPSCs) and improved efficiency in multiple clinically relevant primary immune cell types and at multiple genomic loci implicated for clinical applications with various nuclease editor systems. The high precision and efficiency in chimeric antigen receptor (CAR)-T and natural killer (NK) cells, improved safety, payload flexibility and scalable manufacturability of cssDNA shows potential for future applications of genome engineering.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"25 6 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evan Groover, Elizabeth Njuguna, Kailash Chander Bansal, Anne Muia, Musa Kwehangana, Christopher Simuntala, Richard Lloyd Mills, Emmanuel Kwakye, Pedro Rocha, Josephine Amedu, Eduardo Morillo, Mohana Anita Anthonysamy, A. B. M. Khaldun, Lilian Chimpepo, Massouroudini Akoudjin, D. M. J. B. Senanayake, Dechen Wangmo, Dessalegn Atnafu, Geronima P. Eusebio, Chalinee Kongsawat, Melinda Kliegman
{"title":"A technical approach to global plant genome editing regulation","authors":"Evan Groover, Elizabeth Njuguna, Kailash Chander Bansal, Anne Muia, Musa Kwehangana, Christopher Simuntala, Richard Lloyd Mills, Emmanuel Kwakye, Pedro Rocha, Josephine Amedu, Eduardo Morillo, Mohana Anita Anthonysamy, A. B. M. Khaldun, Lilian Chimpepo, Massouroudini Akoudjin, D. M. J. B. Senanayake, Dechen Wangmo, Dessalegn Atnafu, Geronima P. Eusebio, Chalinee Kongsawat, Melinda Kliegman","doi":"10.1038/s41587-024-02489-5","DOIUrl":"10.1038/s41587-024-02489-5","url":null,"abstract":"The Innovate Genomics Institute brought together regulators from 16 countries to discuss global capacity building for the regulation of genome-edited crops. The workshop provided insights into the suitable use of technical analyses to validate edits and raised future considerations regarding regulation reporting, offering suggestions to help countries meet their objectives in the ever-growing landscape of genome editing techniques.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1773-1780"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Randal A. Serafini, Micaila D. E. Curtis, Stella Alimperti
{"title":"Intellectual property training should be embedded in the biomedical education process","authors":"Randal A. Serafini, Micaila D. E. Curtis, Stella Alimperti","doi":"10.1038/s41587-024-02499-3","DOIUrl":"10.1038/s41587-024-02499-3","url":null,"abstract":"Implementation of intellectual property education in academic institutions can result in increased opportunities for protecting intellectual property and limit costs, but to be successful technology transfer offices must also adapt.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1924-1925"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02499-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}