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}
Pub Date : 2023-10-26DOI: 10.1038/s41587-023-02006-0
Caroline Seydel
As new technologies hit the market, synthetic DNA is available faster and cheaper than ever before. Regulators are preparing to step in to limit opportunities for misuse.
随着新技术进入市场，合成 DNA 的供应比以往任何时候都更快、更便宜。监管机构正准备介入，以限制滥用机会。
{"title":"DNA writing technologies moving toward synthetic genomes","authors":"Caroline Seydel","doi":"10.1038/s41587-023-02006-0","DOIUrl":"10.1038/s41587-023-02006-0","url":null,"abstract":"As new technologies hit the market, synthetic DNA is available faster and cheaper than ever before. Regulators are preparing to step in to limit opportunities for misuse.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 11","pages":"1504-1509"},"PeriodicalIF":46.9,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-02006-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230314","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 : 2023-10-23DOI: 10.1038/s41587-023-02003-3
Using an experimental and computational framework inspired by compressed sensing, we greatly reduced the number of measurements needed to run Perturb-seq. Our compressed Perturb-seq strategy relies on collecting measurements comprising random linear combinations of genetic perturbations, followed by deconvolving the perturbation effects on the transcriptome using sparsity-exploiting algorithms.
{"title":"Compressed Perturb-seq enables highly efficient genetic screens","authors":"","doi":"10.1038/s41587-023-02003-3","DOIUrl":"10.1038/s41587-023-02003-3","url":null,"abstract":"Using an experimental and computational framework inspired by compressed sensing, we greatly reduced the number of measurements needed to run Perturb-seq. Our compressed Perturb-seq strategy relies on collecting measurements comprising random linear combinations of genetic perturbations, followed by deconvolving the perturbation effects on the transcriptome using sparsity-exploiting algorithms.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1194-1195"},"PeriodicalIF":33.1,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691633","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 : 2023-10-23DOI: 10.1038/s41587-023-02021-1
Petar Hristov, Ryan A. Flynn
A recently discovered RNA species on the cell surface is studied by proximity ligation.
通过近距离连接对细胞表面最近发现的一种 RNA 进行研究。
{"title":"Imaging glycosylated RNAs at the subcellular scale","authors":"Petar Hristov, Ryan A. Flynn","doi":"10.1038/s41587-023-02021-1","DOIUrl":"10.1038/s41587-023-02021-1","url":null,"abstract":"A recently discovered RNA species on the cell surface is studied by proximity ligation.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 4","pages":"574-575"},"PeriodicalIF":46.9,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691635","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 : 2023-10-23DOI: 10.1038/s41587-023-01964-9
Douglas Yao, Loic Binan, Jon Bezney, Brooke Simonton, Jahanara Freedman, Chris J. Frangieh, Kushal Dey, Kathryn Geiger-Schuller, Basak Eraslan, Alexander Gusev, Aviv Regev, Brian Cleary
Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique in functional genomics, but they are limited in scale by cost and combinatorial complexity. In this study, we modified the design of Perturb-seq by incorporating algorithms applied to random, low-dimensional observations. Compressed Perturb-seq measures multiple random perturbations per cell or multiple cells per droplet and computationally decompresses these measurements by leveraging the sparse structure of regulatory circuits. Applied to 598 genes in the immune response to bacterial lipopolysaccharide, compressed Perturb-seq achieves the same accuracy as conventional Perturb-seq with an order of magnitude cost reduction and greater power to learn genetic interactions. We identified known and novel regulators of immune responses and uncovered evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing genome-wide association studies. Our framework enables new scales of interrogation for a foundational method in functional genomics. Compressed Perturb-seq incorporates compressed sensing to genetic screening for scalable discovery of genetic interactions.
{"title":"Scalable genetic screening for regulatory circuits using compressed Perturb-seq","authors":"Douglas Yao, Loic Binan, Jon Bezney, Brooke Simonton, Jahanara Freedman, Chris J. Frangieh, Kushal Dey, Kathryn Geiger-Schuller, Basak Eraslan, Alexander Gusev, Aviv Regev, Brian Cleary","doi":"10.1038/s41587-023-01964-9","DOIUrl":"10.1038/s41587-023-01964-9","url":null,"abstract":"Pooled CRISPR screens with single-cell RNA sequencing readout (Perturb-seq) have emerged as a key technique in functional genomics, but they are limited in scale by cost and combinatorial complexity. In this study, we modified the design of Perturb-seq by incorporating algorithms applied to random, low-dimensional observations. Compressed Perturb-seq measures multiple random perturbations per cell or multiple cells per droplet and computationally decompresses these measurements by leveraging the sparse structure of regulatory circuits. Applied to 598 genes in the immune response to bacterial lipopolysaccharide, compressed Perturb-seq achieves the same accuracy as conventional Perturb-seq with an order of magnitude cost reduction and greater power to learn genetic interactions. We identified known and novel regulators of immune responses and uncovered evolutionarily constrained genes with downstream targets enriched for immune disease heritability, including many missed by existing genome-wide association studies. Our framework enables new scales of interrogation for a foundational method in functional genomics. Compressed Perturb-seq incorporates compressed sensing to genetic screening for scalable discovery of genetic interactions.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 8","pages":"1282-1295"},"PeriodicalIF":33.1,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691636","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 : 2023-10-23DOI: 10.1038/s41587-023-02029-7
Matthew Hutson
Biopharma companies debate whether to patent their algorithms for finding medicines.
生物制药公司就是否为其寻找药物的算法申请专利展开了辩论。
{"title":"AI for drug discovery is booming, but who owns the patents?","authors":"Matthew Hutson","doi":"10.1038/s41587-023-02029-7","DOIUrl":"10.1038/s41587-023-02029-7","url":null,"abstract":"Biopharma companies debate whether to patent their algorithms for finding medicines.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 11","pages":"1494-1496"},"PeriodicalIF":46.9,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-02029-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691632","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 : 2023-10-19DOI: 10.1038/s41587-023-01945-y
Hem R. Gurung, Amy J. Heidersbach, Martine Darwish, Pamela Pui Fung Chan, Jenny Li, Maureen Beresini, Oliver A. Zill, Andrew Wallace, Ann-Jay Tong, Dan Hascall, Eric Torres, Andy Chang, Kenny ‘Hei-Wai’ Lou, Yassan Abdolazimi, Christian Hammer, Ana Xavier-Magalhães, Ana Marcu, Samir Vaidya, Daniel D. Le, Ilseyar Akhmetzyanova, Soyoung A. Oh, Amanda J. Moore, Uzodinma N. Uche, Melanie B. Laur, Richard J. Notturno, Peter J. R. Ebert, Craig Blanchette, Benjamin Haley, Christopher M. Rose
The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen–human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide–HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope–HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope–HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies. A large resource of shared tumor neoepitopes aims to accelerate cancer immunotherapy.
{"title":"Systematic discovery of neoepitope–HLA pairs for neoantigens shared among patients and tumor types","authors":"Hem R. Gurung, Amy J. Heidersbach, Martine Darwish, Pamela Pui Fung Chan, Jenny Li, Maureen Beresini, Oliver A. Zill, Andrew Wallace, Ann-Jay Tong, Dan Hascall, Eric Torres, Andy Chang, Kenny ‘Hei-Wai’ Lou, Yassan Abdolazimi, Christian Hammer, Ana Xavier-Magalhães, Ana Marcu, Samir Vaidya, Daniel D. Le, Ilseyar Akhmetzyanova, Soyoung A. Oh, Amanda J. Moore, Uzodinma N. Uche, Melanie B. Laur, Richard J. Notturno, Peter J. R. Ebert, Craig Blanchette, Benjamin Haley, Christopher M. Rose","doi":"10.1038/s41587-023-01945-y","DOIUrl":"10.1038/s41587-023-01945-y","url":null,"abstract":"The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen–human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide–HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope–HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope–HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies. A large resource of shared tumor neoepitopes aims to accelerate cancer immunotherapy.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 7","pages":"1107-1117"},"PeriodicalIF":33.1,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680200","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 : 2023-10-18DOI: 10.1038/s41587-023-02025-x
Julia M. Gauglitz, Kiana A. West, Wout Bittremieux, Candace L. Williams, Kelly C. Weldon, Morgan Panitchpakdi, Francesca Di Ottavio, Christine M. Aceves, Elizabeth Brown, Nicole C. Sikora, Alan K. Jarmusch, Cameron Martino, Anupriya Tripathi, Michael J. Meehan, Kathleen Dorrestein, Justin P. Shaffer, Roxana Coras, Fernando Vargas, Lindsay DeRight Goldasich, Tara Schwartz, MacKenzie Bryant, Gregory Humphrey, Abigail J. Johnson, Katharina Spengler, Pedro Belda-Ferre, Edgar Diaz, Daniel McDonald, Qiyun Zhu, Emmanuel O. Elijah, Mingxun Wang, Clarisse Marotz, Kate E. Sprecher, Daniela Vargas-Robles, Dana Withrow, Gail Ackermann, Lourdes Herrera, Barry J. Bradford, Lucas Maciel Mauriz Marques, Juliano Geraldo Amaral, Rodrigo Moreira Silva, Flavio Protasio Veras, Thiago Mattar Cunha, Rene Donizeti Ribeiro Oliveira, Paulo Louzada-Junior, Robert H. Mills, Paulina K. Piotrowski, Stephanie L. Servetas, Sandra M. Da Silva, Christina M. Jones, Nancy J. Lin, Katrice A. Lippa, Scott A. Jackson, Rima Kaddurah Daouk, Douglas Galasko, Parambir S. Dulai, Tatyana I. Kalashnikova, Curt Wittenberg, Robert Terkeltaub, Megan M. Doty, Jae H. Kim, Kyung E. Rhee, Julia Beauchamp-Walters, Kenneth P. Wright Jr, Maria Gloria Dominguez-Bello, Mark Manary, Michelli F. Oliveira, Brigid S. Boland, Norberto Peporine Lopes, Monica Guma, Austin D. Swafford, Rachel J. Dutton, Rob Knight, Pieter C. Dorrestein
{"title":"Author Correction: Enhancing untargeted metabolomics using metadata-based source annotation","authors":"Julia M. Gauglitz, Kiana A. West, Wout Bittremieux, Candace L. Williams, Kelly C. Weldon, Morgan Panitchpakdi, Francesca Di Ottavio, Christine M. Aceves, Elizabeth Brown, Nicole C. Sikora, Alan K. Jarmusch, Cameron Martino, Anupriya Tripathi, Michael J. Meehan, Kathleen Dorrestein, Justin P. Shaffer, Roxana Coras, Fernando Vargas, Lindsay DeRight Goldasich, Tara Schwartz, MacKenzie Bryant, Gregory Humphrey, Abigail J. Johnson, Katharina Spengler, Pedro Belda-Ferre, Edgar Diaz, Daniel McDonald, Qiyun Zhu, Emmanuel O. Elijah, Mingxun Wang, Clarisse Marotz, Kate E. Sprecher, Daniela Vargas-Robles, Dana Withrow, Gail Ackermann, Lourdes Herrera, Barry J. Bradford, Lucas Maciel Mauriz Marques, Juliano Geraldo Amaral, Rodrigo Moreira Silva, Flavio Protasio Veras, Thiago Mattar Cunha, Rene Donizeti Ribeiro Oliveira, Paulo Louzada-Junior, Robert H. Mills, Paulina K. Piotrowski, Stephanie L. Servetas, Sandra M. Da Silva, Christina M. Jones, Nancy J. Lin, Katrice A. Lippa, Scott A. Jackson, Rima Kaddurah Daouk, Douglas Galasko, Parambir S. Dulai, Tatyana I. Kalashnikova, Curt Wittenberg, Robert Terkeltaub, Megan M. Doty, Jae H. Kim, Kyung E. Rhee, Julia Beauchamp-Walters, Kenneth P. Wright Jr, Maria Gloria Dominguez-Bello, Mark Manary, Michelli F. Oliveira, Brigid S. Boland, Norberto Peporine Lopes, Monica Guma, Austin D. Swafford, Rachel J. Dutton, Rob Knight, Pieter C. Dorrestein","doi":"10.1038/s41587-023-02025-x","DOIUrl":"10.1038/s41587-023-02025-x","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"41 11","pages":"1656-1656"},"PeriodicalIF":46.9,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-023-02025-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680197","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 : 2023-10-18DOI: 10.1038/s41587-023-02026-w
Daniel McDonald, Yueyu Jiang, Metin Balaban, Kalen Cantrell, Qiyun Zhu, Antonio Gonzalez, James T. Morton, Giorgia Nicolaou, Donovan H. Parks, Søren M. Karst, Mads Albertsen, Philip Hugenholtz, Todd DeSantis, Se Jin Song, Andrew Bartko, Aki S. Havulinna, Pekka Jousilahti, Susan Cheng, Michael Inouye, Teemu Niiranen, Mohit Jain, Veikko Salomaa, Leo Lahti, Siavash Mirarab, Rob Knight
{"title":"Author Correction: Greengenes2 unifies microbial data in a single reference tree","authors":"Daniel McDonald, Yueyu Jiang, Metin Balaban, Kalen Cantrell, Qiyun Zhu, Antonio Gonzalez, James T. Morton, Giorgia Nicolaou, Donovan H. Parks, Søren M. Karst, Mads Albertsen, Philip Hugenholtz, Todd DeSantis, Se Jin Song, Andrew Bartko, Aki S. Havulinna, Pekka Jousilahti, Susan Cheng, Michael Inouye, Teemu Niiranen, Mohit Jain, Veikko Salomaa, Leo Lahti, Siavash Mirarab, Rob Knight","doi":"10.1038/s41587-023-02026-w","DOIUrl":"10.1038/s41587-023-02026-w","url":null,"abstract":"","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"42 5","pages":"813-813"},"PeriodicalIF":46.9,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11098728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49680199","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}
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