ArticlebioRxiv : the preprint server for biology2025
Installation of Dominant-Negative Mutations in
Bryce J Wick, Mitchell G Kluesner, Nicholas J Slipek, Joseph G Skeate, Ethan M Niemeyer, Beau R Webber, Branden S Moriarity
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
7 authors.
Bryce J WickDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Mitchell G KluesnerMolecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Ethan M NiemeyerDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Funding
Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller · 1998 to 2026
$100.4MUse of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI ELLEN L. GOODE · 2009 to 2026
$37.0MProject 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CAIRO, MITCHELL S., CRIPE, TIMOTHY P · 2019 to 2023
$12.1MTRAINING IN HEMOGLOBIN &CELL MEMBRANE RESEARCHT32HL007062 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller, Gregory M Vercellotti · 1985 to 2026
$10.3MProject 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2021 to 2025
$9.4MTECH CoreU54CA268069 · NCI · UNIVERSITY OF MINNESOTA · PI David J. Odde · 2022 to 2026
$8.2MSCGE Disease Models Studies Supplement: Evaluation of prime editing for the amelioration of alpha-1-antitrypsin deficiency in murine and porcine models.U24OD026641 · OD · RECOMBINETICS, INC. · PI CARLSON, DANIEL FRED · 2018 to 2022
$4.1MActivated NK CAR Cells to Cure HIVR01AI161017 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S, SKINNER, PAMELA J · 2021 to 2025
$3.8MEngineered B Cells as a Universal Platform for the Treatment of EnzymopathiesR01AI146009 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S · 2020 to 2024
$1.9MMultiplex Engineered Human Lymphocytes for Therapeutic Protein DeliveryR21AI163731 · NIAID · UNIVERSITY OF MINNESOTA · PI WEBBER, BEAU RICHARD · 2021 to 2022
$426kDetermining the cell of origin in Ewing sarcoma through genomic analysisR21CA237789 · NCI · UNIVERSITY OF MINNESOTA · PI SPECTOR, LOGAN G., WEBBER, BEAU RICHARD · 2020 to 2021
$396kOvercoming Antigen-Low Tumor Escape in Non Small Cell Lung Cancer with Chimeric TCR T Cell TherapyF30CA305905 · NCI · UNIVERSITY OF WASHINGTON · PI Mitchell George Kluesner · 2025 to 2026
$97kNCI NIH HHS F30 CA305905NCI NIH HHS P01 CA254849NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA136393NCI NIH HHS R21 CA237789NCI NIH HHS U54 CA232561NCI NIH HHS U54 CA268069NHLBI NIH HHS T32 HL007062NIAID NIH HHS R01 AI146009NIAID NIH HHS R01 AI161017NIAID NIH HHS R21 AI163731NIH HHS U24 OD026641
6 · The paper itselfAbstract
Adoptive cell transfer (ACT) of engineered T cells is effective against B-cell malignancies but has faltered against solid tumors due to the immunosuppressive tumor microenvironment (TME). FASL and TGFβ are key mediators of T cell dysfunction in the TME and overexpressing dominant negative (dn) forms of their receptors in T cells increases anti-tumor efficacy in solid tumor models. However, an approach which directly targets the endogenous genes would be more amenable to multiplex editing and reduce competition with WT alleles. Here, we employ base editing (BE) in primary human T cells to install naturally occurring dominant negative
Indexed as
base editorscancer immunotherapyCAR TDominant-negative mutationsT cells
Identifiers
PMID41000687
PMCPMC12458180
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