Evidence map›Paper›PMID 31745080›Full record

ArticleNature communications2019

Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors.

Beau R Webber, Cara-Lin Lonetree, Mitchell G Kluesner, Matthew J Johnson, Emily J Pomeroy, Miechaleen D Diers, Walker S Lahr, Garrett M Draper, Nicholas J Slipek, Branden A Smeester and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 171 papers.

0numbers the graph read from it
0cells of the map it votes in
171citing papers in PubMed
8.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

171 citing papers in PubMed, 216 citations in OpenAlex.

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  10. Efficient multiplex non-viral engineering and expansion of polyclonal γδ CAR-T cells for immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  11. Review
  12. Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
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  15. Article
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111 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Beau R WebberDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-3950-8747
Cara-Lin LonetreeDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Mitchell G KluesnerDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-5828-9204
Matthew J JohnsonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-1313-1742
Emily J PomeroyDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0001-7690-3570
Miechaleen D DiersDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Walker S LahrDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Garrett M DraperDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Nicholas J SlipekDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0003-2664-6507
Branden A SmeesterDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Klaus N LovendahlDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-3871-3570
Amber N McElroyDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Wendy R GordonDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.
Mark J OsbornDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Branden S MoriarityDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA. mori0164@umn.edu.
University of Minnesota · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
IMMUNOLOGY TRAINING PROGRAMT32AI007313 · NIAID · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Carla Rothlin · 1989 to 2026
$5.7M
Mechanism and modulation of Amyloid Precursor Protein proteolysisR35GM119483 · NIGMS · UNIVERSITY OF MINNESOTA · PI WENDY RYAN GORDON · 2016 to 2026
$4.6M
Engineered Systems for Conditional and Temporal Gene Manipulation in Primary Lymphohematopoietic CellsR03AI144840 · NIAID · UNIVERSITY OF MINNESOTA · PI MORIARITY, BRANDEN S, WEBBER, BEAU RICHARD · 2019 to 2020
$154k
NCI NIH HHS P30 CA077598NIAID NIH HHS R03 AI144840NIAID NIH HHS T32 AI007313NIGMS NIH HHS R35 GM119483
6 · The paper itself

Abstract

The fusion of genome engineering and adoptive cellular therapy holds immense promise for the treatment of genetic disease and cancer. Multiplex genome engineering using targeted nucleases can be used to increase the efficacy and broaden the application of such therapies but carries safety risks associated with unintended genomic alterations and genotoxicity. Here, we apply base editor technology for multiplex gene modification in primary human T cells in support of an allogeneic CAR-T platform and demonstrate that base editor can mediate highly efficient multiplex gene disruption with minimal double-strand break induction. Importantly, multiplex base edited T cells exhibit improved expansion and lack double strand break-induced translocations observed in T cells edited with Cas9 nuclease. Our findings highlight base editor as a powerful platform for genetic modification of therapeutically relevant primary cell types.

Indexed as

CRISPR-Cas SystemsDNA Breaks, Double-StrandedCell EngineeringCells, CulturedGene EditingHigh-Throughput Nucleotide SequencingHumansImmunotherapy, AdoptiveReproducibility of ResultsT-Lymphocytes

Identifiers

PMID31745080
PMCPMC6864045
OpenAlexW2991627551

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.