Pub Date : 2025-02-17DOI: 10.1038/s41587-025-02568-1
Chunwei Zheng, Gangming Zhang, Lilia J. Dean, Erik J. Sontheimer, Wen Xue
Reverse transcriptase (RT) has been shown to play a role in double-strand break repair in bacteria, yet the impact of the RT component of prime editors (PEs) on normal mammalian cellular functions is unclear. Here we show that overexpressed RT or PE increases short insertions and diminishes homology-directed repair following Cas9 cleavage at multiple loci in multiple cell lines. Live-cell imaging shows that RT and PEs are rapidly recruited to laser-induced DNA damage sites and promote endogenous repair, independent of known DNA damage sensors. Interestingly, RT–mCherry partially impairs green fluorescent protein–PARP1 recruitment. A compact PE without an RNase H domain shows reduced DNA repair activity and may therefore be more suitable for clinical application. These data reveal a role for untethered RT or the RT domain of PEs in the repair of chromosomal breaks, calling for evaluation of the long-term effect of PEs and retroviral RT in mammalian cells.
{"title":"The reverse transcriptase domain of prime editors contributes to DNA repair in mammalian cells","authors":"Chunwei Zheng, Gangming Zhang, Lilia J. Dean, Erik J. Sontheimer, Wen Xue","doi":"10.1038/s41587-025-02568-1","DOIUrl":"https://doi.org/10.1038/s41587-025-02568-1","url":null,"abstract":"<p>Reverse transcriptase (RT) has been shown to play a role in double-strand break repair in bacteria, yet the impact of the RT component of prime editors (PEs) on normal mammalian cellular functions is unclear. Here we show that overexpressed RT or PE increases short insertions and diminishes homology-directed repair following Cas9 cleavage at multiple loci in multiple cell lines. Live-cell imaging shows that RT and PEs are rapidly recruited to laser-induced DNA damage sites and promote endogenous repair, independent of known DNA damage sensors. Interestingly, RT–mCherry partially impairs green fluorescent protein–PARP1 recruitment. A compact PE without an RNase H domain shows reduced DNA repair activity and may therefore be more suitable for clinical application. These data reveal a role for untethered RT or the RT domain of PEs in the repair of chromosomal breaks, calling for evaluation of the long-term effect of PEs and retroviral RT in mammalian cells.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"3 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427077","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}
Pub Date : 2025-02-14DOI: 10.1038/s41587-025-02581-4
{"title":"Gene and cell therapies for Parkinson’s make headway","authors":"","doi":"10.1038/s41587-025-02581-4","DOIUrl":"10.1038/s41587-025-02581-4","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 2","pages":"156-156"},"PeriodicalIF":33.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417943","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}
Pub Date : 2025-02-14DOI: 10.1038/s41587-025-02578-z
{"title":"Colossal raises $200 million to bring back the dodo","authors":"","doi":"10.1038/s41587-025-02578-z","DOIUrl":"10.1038/s41587-025-02578-z","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 2","pages":"155-155"},"PeriodicalIF":33.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417947","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}
Pub Date : 2025-02-14DOI: 10.1038/s41587-024-02549-w
Soma S. R. Banik, Xiaoxiang Deng, Edgar Davidson, Ulrich Storz, Benjamin J. Doranz
Patent protection for therapeutic monoclonal antibodies requires a fundamental shift in strategy following Amgen v. Sanofi, which invalidated broad functional claims for antibody genera in the USA.
在安进诉赛诺菲案(Amgen v. Sanofi)之后,治疗性单克隆抗体的专利保护需要从根本上改变策略。
{"title":"Redefining antibody patent protection using paratope mapping and CDR-scanning","authors":"Soma S. R. Banik, Xiaoxiang Deng, Edgar Davidson, Ulrich Storz, Benjamin J. Doranz","doi":"10.1038/s41587-024-02549-w","DOIUrl":"10.1038/s41587-024-02549-w","url":null,"abstract":"Patent protection for therapeutic monoclonal antibodies requires a fundamental shift in strategy following Amgen v. Sanofi, which invalidated broad functional claims for antibody genera in the USA.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 2","pages":"170-174"},"PeriodicalIF":33.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02549-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417950","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}
Pub Date : 2025-02-14DOI: 10.1038/s41587-025-02564-5
Ben Johnson
Companies are striking unconventional benefit-sharing agreements with national governments to scour planet hotspots, gathering thousands of new DNA and protein sequences to develop into new, commercially useful molecules.
{"title":"AI biotechs launch bioprospecting expeditions with Indigenous groups, agree to share benefits","authors":"Ben Johnson","doi":"10.1038/s41587-025-02564-5","DOIUrl":"10.1038/s41587-025-02564-5","url":null,"abstract":"Companies are striking unconventional benefit-sharing agreements with national governments to scour planet hotspots, gathering thousands of new DNA and protein sequences to develop into new, commercially useful molecules.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 2","pages":"154-156"},"PeriodicalIF":33.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-025-02564-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417949","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}