Pub Date : 2023-11-10DOI: 10.1038/s41587-023-02011-3
Michael Yan, Giovanni G. Cerri, Fabio Y. Moraes
ChatGPT holds transformative potential for medicine across clinical, research and educational domains.
ChatGPT 在医学的临床、研究和教育领域都具有变革潜力。
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Pub Date : 2023-11-06DOI: 10.1038/s41587-023-01974-7
Jenny A. Greig, Kelly M. Martins, Camilo Breton, R. Jason Lamontagne, Yanqing Zhu, Zhenning He, John White, Jing-Xu Zhu, Jessica A. Chichester, Qi Zheng, Zhe Zhang, Peter Bell, Lili Wang, James M. Wilson
The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state. More than 10% of hepatocytes contained single nuclear domains of vector DNA that persisted despite the loss of transgene expression. Greater reductions in vector DNA and RNA were observed with immunogenic transgenes. Genomic integration of vector sequences, including complex concatemeric structures, were detected in 1 out of 100 cells at broadly distributed loci that were not in proximity to genes associated with hepatocellular carcinoma. Our studies suggest that AAV-mediated transgene expression in primate hepatocytes occurs in two phases: high but short-lived expression from episomal genomes, followed by much lower but stable expression, likely from integrated vectors. Long-term expression of AAV transgenes in macaque liver is traced to integrated vectors.
{"title":"Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration","authors":"Jenny A. Greig, Kelly M. Martins, Camilo Breton, R. Jason Lamontagne, Yanqing Zhu, Zhenning He, John White, Jing-Xu Zhu, Jessica A. Chichester, Qi Zheng, Zhe Zhang, Peter Bell, Lili Wang, James M. Wilson","doi":"10.1038/s41587-023-01974-7","DOIUrl":"10.1038/s41587-023-01974-7","url":null,"abstract":"The development of liver-based adeno-associated virus (AAV) gene therapies is facing concerns about limited efficiency and durability of transgene expression. We evaluated nonhuman primates following intravenous dosing of AAV8 and AAVrh10 vectors for over 2 years to better define the mechanism(s) of transduction that affect performance. High transduction of non-immunogenic transgenes was achieved, although expression declined over the first 90 days to reach a lower but stable steady state. More than 10% of hepatocytes contained single nuclear domains of vector DNA that persisted despite the loss of transgene expression. Greater reductions in vector DNA and RNA were observed with immunogenic transgenes. Genomic integration of vector sequences, including complex concatemeric structures, were detected in 1 out of 100 cells at broadly distributed loci that were not in proximity to genes associated with hepatocellular carcinoma. Our studies suggest that AAV-mediated transgene expression in primate hepatocytes occurs in two phases: high but short-lived expression from episomal genomes, followed by much lower but stable expression, likely from integrated vectors. Long-term expression of AAV transgenes in macaque liver is traced to integrated vectors.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1232-1242"},"PeriodicalIF":33.1,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-01974-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71484214","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 : 2023-11-02DOI: 10.1038/s41587-023-02045-7
Quantum dots won the Nobel Prize, but proved to be a miss in the biomedical space.
量子点获得了诺贝尔奖，但在生物医学领域却被证明是一个失误。
{"title":"All that Nobel glitters is not biotech gold","authors":"","doi":"10.1038/s41587-023-02045-7","DOIUrl":"10.1038/s41587-023-02045-7","url":null,"abstract":"Quantum dots won the Nobel Prize, but proved to be a miss in the biomedical space.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 11","pages":"1489-1489"},"PeriodicalIF":46.9,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-02045-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425401","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 : 2023-10-30DOI: 10.1038/s41587-023-01932-3
Janet K. Jansson, Ryan McClure, Robert G. Egbert
Recent advances in microbial ecology and synthetic biology have the potential to mitigate damage caused by anthropogenic activities that are deleteriously impacting Earth’s soil ecosystems. Here, we discuss challenges and opportunities for harnessing natural and synthetic soil microbial communities, focusing on plant growth promotion under different scenarios. We explore current needs for microbial solutions in soil ecosystems, how these solutions are being developed and applied, and the potential for new biotechnology breakthroughs to tailor and target microbial products for specific applications. We highlight several scientific and technological advances in soil microbiome engineering, including characterization of microbes that impact soil ecosystems, directing how microbes assemble to interact in soil environments, and the developing suite of gene-engineering approaches. This Review underscores the need for an interdisciplinary approach to understand the composition, dynamics and deployment of beneficial soil microbiomes to drive efforts to mitigate or reverse environmental damage by restoring and protecting healthy soil ecosystems. Challenges and opportunities for engineering and studying the soil microbiome are discussed.
{"title":"Soil microbiome engineering for sustainability in a changing environment","authors":"Janet K. Jansson, Ryan McClure, Robert G. Egbert","doi":"10.1038/s41587-023-01932-3","DOIUrl":"10.1038/s41587-023-01932-3","url":null,"abstract":"Recent advances in microbial ecology and synthetic biology have the potential to mitigate damage caused by anthropogenic activities that are deleteriously impacting Earth’s soil ecosystems. Here, we discuss challenges and opportunities for harnessing natural and synthetic soil microbial communities, focusing on plant growth promotion under different scenarios. We explore current needs for microbial solutions in soil ecosystems, how these solutions are being developed and applied, and the potential for new biotechnology breakthroughs to tailor and target microbial products for specific applications. We highlight several scientific and technological advances in soil microbiome engineering, including characterization of microbes that impact soil ecosystems, directing how microbes assemble to interact in soil environments, and the developing suite of gene-engineering approaches. This Review underscores the need for an interdisciplinary approach to understand the composition, dynamics and deployment of beneficial soil microbiomes to drive efforts to mitigate or reverse environmental damage by restoring and protecting healthy soil ecosystems. Challenges and opportunities for engineering and studying the soil microbiome are discussed.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 12","pages":"1716-1728"},"PeriodicalIF":46.9,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413229","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 : 2023-10-30DOI: 10.1038/s41587-023-02022-0
Cormac Sheridan
Armed with gene technologies and CAR-Ts, scientists are attempting to eliminate viruses that escape immune detection and lurk in tissues for years.
在基因技术和 CAR-Ts 的帮助下，科学家们正试图消灭那些逃避免疫检测并在组织中潜伏多年的病毒。
{"title":"Can gene editing drive out HIV and hepatitis viruses from inside cells?","authors":"Cormac Sheridan","doi":"10.1038/s41587-023-02022-0","DOIUrl":"10.1038/s41587-023-02022-0","url":null,"abstract":"Armed with gene technologies and CAR-Ts, scientists are attempting to eliminate viruses that escape immune detection and lurk in tissues for years.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 11","pages":"1491-1493"},"PeriodicalIF":46.9,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-02022-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413228","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 : 2023-10-26DOI: 10.1038/s41587-023-01981-8
Magdi Elsallab, Marcela V. Maus
Chimeric antigen receptor (CAR) T cells are changing the therapeutic landscape for hematological malignancies. To date, all six CAR T cell products approved by the US Food and Drug Administration (FDA) are autologous and centrally manufactured. As the numbers of approved products and indications continue to grow, new strategies to increase cell-manufacturing capacity are urgently needed to ensure patient access. Distributed manufacturing at the point of care or at other local manufacturing sites would go a long way toward meeting the rising demand. To ensure successful implementation, it is imperative to harness novel technologies to achieve uniform product quality across geographically dispersed facilities. This includes the use of automated cell-production systems, in-line sensors and process simulation for enhanced quality control and efficient supply chain management. A comprehensive effort to understand the critical quality attributes of CAR T cells would enable better definition of widely attainable release criteria. To supplement oversight by national regulatory agencies, we recommend expansion of the role of accreditation bodies. Moreover, regulatory standards may need to be amended to accommodate the unique characteristics of distributed manufacturing models. Shortages of CAR T cells should be alleviated by distributed manufacturing, according to Elsallab and Maus.
{"title":"Expanding access to CAR T cell therapies through local manufacturing","authors":"Magdi Elsallab, Marcela V. Maus","doi":"10.1038/s41587-023-01981-8","DOIUrl":"10.1038/s41587-023-01981-8","url":null,"abstract":"Chimeric antigen receptor (CAR) T cells are changing the therapeutic landscape for hematological malignancies. To date, all six CAR T cell products approved by the US Food and Drug Administration (FDA) are autologous and centrally manufactured. As the numbers of approved products and indications continue to grow, new strategies to increase cell-manufacturing capacity are urgently needed to ensure patient access. Distributed manufacturing at the point of care or at other local manufacturing sites would go a long way toward meeting the rising demand. To ensure successful implementation, it is imperative to harness novel technologies to achieve uniform product quality across geographically dispersed facilities. This includes the use of automated cell-production systems, in-line sensors and process simulation for enhanced quality control and efficient supply chain management. A comprehensive effort to understand the critical quality attributes of CAR T cells would enable better definition of widely attainable release criteria. To supplement oversight by national regulatory agencies, we recommend expansion of the role of accreditation bodies. Moreover, regulatory standards may need to be amended to accommodate the unique characteristics of distributed manufacturing models. Shortages of CAR T cells should be alleviated by distributed manufacturing, according to Elsallab and Maus.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 12","pages":"1698-1708"},"PeriodicalIF":46.9,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230315","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}
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