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  1. Article ; Online: CRISPR screens decode cancer cell pathways that trigger γδ T cell detection.

    Mamedov, Murad R / Vedova, Shane / Freimer, Jacob W / Sahu, Avinash Das / Ramesh, Amrita / Arce, Maya M / Meringa, Angelo D / Ota, Mineto / Chen, Peixin Amy / Hanspers, Kristina / Nguyen, Vinh Q / Takeshima, Kirsten A / Rios, Anne C / Pritchard, Jonathan K / Kuball, Jürgen / Sebestyen, Zsolt / Adams, Erin J / Marson, Alexander

    Nature

    2023  Volume 621, Issue 7977, Page(s) 188–195

    Abstract: γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen ... ...

    Abstract γδ T cells are potent anticancer effectors with the potential to target tumours broadly, independent of patient-specific neoantigens or human leukocyte antigen background
    MeSH term(s) Humans ; AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Cell Line ; Cell Membrane/metabolism ; CRISPR-Cas Systems ; Gene Editing ; Neoplasms/genetics ; Neoplasms/immunology ; Neoplasms/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemical Substances AMP-Activated Protein Kinases (EC 2.7.11.31) ; BTN2A1 protein, human ; BTN3A1 protein, human ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2023-08-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06482-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails.

    Shy, Brian R / Vykunta, Vivasvan S / Ha, Alvin / Talbot, Alexis / Roth, Theodore L / Nguyen, David N / Pfeifer, Wolfgang G / Chen, Yan Yi / Blaeschke, Franziska / Shifrut, Eric / Vedova, Shane / Mamedov, Murad R / Chung, Jing-Yi Jing / Li, Hong / Yu, Ruby / Wu, David / Wolf, Jeffrey / Martin, Thomas G / Castro, Carlos E /
    Ye, Lumeng / Esensten, Jonathan H / Eyquem, Justin / Marson, Alexander

    Nature biotechnology

    2022  Volume 41, Issue 4, Page(s) 521–531

    Abstract: Enhancing CRISPR-mediated site-specific transgene insertion efficiency by homology-directed repair (HDR) using high concentrations of double-stranded DNA (dsDNA) with Cas9 target sequences (CTSs) can be toxic to primary cells. Here, we develop single- ... ...

    Abstract Enhancing CRISPR-mediated site-specific transgene insertion efficiency by homology-directed repair (HDR) using high concentrations of double-stranded DNA (dsDNA) with Cas9 target sequences (CTSs) can be toxic to primary cells. Here, we develop single-stranded DNA (ssDNA) HDR templates (HDRTs) incorporating CTSs with reduced toxicity that boost knock-in efficiency and yield by an average of around two- to threefold relative to dsDNA CTSs. Using small-molecule combinations that enhance HDR, we could further increase knock-in efficiencies by an additional roughly two- to threefold on average. Our method works across a variety of target loci, knock-in constructs and primary human cell types, reaching HDR efficiencies of >80-90%. We demonstrate application of this approach for both pathogenic gene variant modeling and gene-replacement strategies for IL2RA and CTLA4 mutations associated with Mendelian disorders. Finally, we develop a good manufacturing practice (GMP)-compatible process for nonviral chimeric antigen receptor-T cell manufacturing, with knock-in efficiencies (46-62%) and yields (>1.5 × 10
    MeSH term(s) Humans ; CRISPR-Cas Systems/genetics ; DNA, Single-Stranded/genetics ; Genome ; Recombinational DNA Repair ; Mutation ; DNA ; Gene Editing ; DNA End-Joining Repair
    Chemical Substances DNA, Single-Stranded ; DNA (9007-49-2)
    Language English
    Publishing date 2022-08-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1311932-1
    ISSN 1546-1696 ; 1087-0156
    ISSN (online) 1546-1696
    ISSN 1087-0156
    DOI 10.1038/s41587-022-01418-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: RASA2 ablation in T cells boosts antigen sensitivity and long-term function.

    Carnevale, Julia / Shifrut, Eric / Kale, Nupura / Nyberg, William A / Blaeschke, Franziska / Chen, Yan Yi / Li, Zhongmei / Bapat, Sagar P / Diolaiti, Morgan E / O'Leary, Patrick / Vedova, Shane / Belk, Julia / Daniel, Bence / Roth, Theodore L / Bachl, Stefanie / Anido, Alejandro Allo / Prinzing, Brooke / Ibañez-Vega, Jorge / Lange, Shannon /
    Haydar, Dalia / Luetke-Eversloh, Marie / Born-Bony, Maelys / Hegde, Bindu / Kogan, Scott / Feuchtinger, Tobias / Okada, Hideho / Satpathy, Ansuman T / Shannon, Kevin / Gottschalk, Stephen / Eyquem, Justin / Krenciute, Giedre / Ashworth, Alan / Marson, Alexander

    Nature

    2022  Volume 609, Issue 7925, Page(s) 174–182

    Abstract: The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory ... ...

    Abstract The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints
    MeSH term(s) Animals ; Antigens, Neoplasm/immunology ; Bone Marrow ; CRISPR-Cas Systems ; Disease Models, Animal ; Gene Knockdown Techniques ; Humans ; Immunotherapy, Adoptive ; Leukemia/immunology ; Leukemia/pathology ; Leukemia/therapy ; Mice ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Receptors, Antigen, T-Cell/immunology ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Time Factors ; Xenograft Model Antitumor Assays ; ras GTPase-Activating Proteins/deficiency ; ras GTPase-Activating Proteins/genetics
    Chemical Substances Antigens, Neoplasm ; RASA2 protein, human ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; ras GTPase-Activating Proteins
    Language English
    Publishing date 2022-08-24
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-022-05126-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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