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}
{"title":"Discovering the crucial function of long noncoding RNAs","authors":"Iris Marchal","doi":"10.1038/s41587-024-02509-4","DOIUrl":"10.1038/s41587-024-02509-4","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1793-1793"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809375","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":"Evo learns biological complexity from the molecular to genome scale","authors":"Iris Marchal","doi":"10.1038/s41587-024-02514-7","DOIUrl":"10.1038/s41587-024-02514-7","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1793-1793"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809371","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":"Stem cells","authors":"","doi":"10.1038/s41587-024-02496-6","DOIUrl":"10.1038/s41587-024-02496-6","url":null,"abstract":"Recent patents relating to compositions, methods of preparation and use of stem cells.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1792-1792"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809373","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":"CRISPR unlocks a sweet tomato that keeps its size","authors":"Iris Marchal","doi":"10.1038/s41587-024-02510-x","DOIUrl":"10.1038/s41587-024-02510-x","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 12","pages":"1793-1793"},"PeriodicalIF":33.1,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809372","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}