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Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.
Blaeschke, Franziska; Chen, Yan Yi; Apathy, Ryan; Daniel, Bence; Chen, Andy Y; Chen, Peixin Amy; Sandor, Katalin; Zhang, Wenxi; Li, Zhongmei; Mowery, Cody T; Yamamoto, Tori N; Nyberg, William A; To, Angela; Yu, Ruby; Bueno, Raymund; Kim, Min Cheol; Schmidt, Ralf; Goodman, Daniel B; Feuchtinger, Tobias; Eyquem, Justin; Jimmie Ye, Chun; Carnevale, Julia; Satpathy, Ansuman T; Shifrut, Eric; Roth, Theodore L; Marson, Alexander.
Afiliação
  • Blaeschke F; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Chen YY; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Apathy R; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Daniel B; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Center for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
  • Chen AY; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • Chen PA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Sandor K; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Zhang W; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA.
  • Li Z; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Mowery CT; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Yamamoto TN; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Nyberg WA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • To A; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Yu R; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Bueno R; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.
  • Kim MC; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA.
  • Schmidt R; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Goodman DB; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunothera
  • Feuchtinger T; Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich 80337, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich 80336, Germany; National Center for Infection Research (DZIF), Munich 8
  • Eyquem J; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for
  • Jimmie Ye C; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for
  • Carnevale J; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; UCSF Helen Di
  • Satpathy AT; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94129, USA; Program in Immunology, Stanford Unive
  • Shifrut E; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Roth TL; Department of Pathology, Stanford University, Stanford, CA 94305, USA. Electronic address: troth@stanford.edu.
  • Marson A; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics (IHG), University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, Uni
Cell ; 186(19): 4216-4234.e33, 2023 09 14.
Article em En | MEDLINE | ID: mdl-37714135
ABSTRACT
Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors (SRs). Over 30 ModPoKI screens across human TCR- and CAR-T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically stimulated CAR-T cells and anti-cancer function in vitro and in vivo. ModPoKI's modularity allowed us to generate an ∼10,000-member library of TF combinations. Non-viral KI of a combined BATF-TFAP4 polycistronic construct enhanced fitness. Overexpressed BATF and TFAP4 co-occupy and regulate key gene targets to reprogram T cell function. ModPoKI facilitates the discovery of complex gene constructs to program cellular functions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Exercício Físico / Terapia Baseada em Transplante de Células e Tecidos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Exercício Físico / Terapia Baseada em Transplante de Células e Tecidos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos