Evidence map›Paper›PMID 36993359›Full record

ArticlebioRxiv : the preprint server for biology2023

Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells.

Connor A Tsuchida, Nadav Brandes, Raymund Bueno, Marena Trinidad, Thomas Mazumder, Bingfei Yu, Byungjin Hwang, Christopher Chang, Jamin Liu, Yang Sun and 12 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 15 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 10 institutions in 2 countries.

Connor A TsuchidaUniversity of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Nadav BrandesDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Raymund BuenoDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Marena TrinidadInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Thomas MazumderDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Bingfei YuCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Byungjin HwangDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Christopher ChangBiomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
Jamin LiuUniversity of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Yang SunDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Caitlin R HopkinsAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kevin R ParkerCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Yanyan QiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Ansuman T SatpathyParker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
Edward A StadtmauerAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jamie H D CateDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Justin EyquemDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Joseph A FraiettaAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Carl H JuneAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Chun Jimmie YeUniversity of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
Jennifer A DoudnaUniversity of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
University of California, San Francisco · USGladstone Institutes · USParker Institute for Cancer Immunotherapy · USQB3 · USEnable Biosciences (United States) · USHoward Hughes Medical Institute · USInnovative Genomics Institute · USMaxygen (United States) · USStanford University · USUniversity of Pennsylvania · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
The Role of the Ribosome in the Accuracy of TranslationR01GM065050 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2001 to 2022
$7.4M
LncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4M
Genetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5M
Expanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0M
Fine mapping rheumatic disease variants using functional genomic sequencingR01AR071522 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2017 to 2020
$1.5M
Characterization and engineering of a compact genome editor for adeno-associated virus delivery to correct mutations causing cystic fibrosisF31HL156468 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI TSUCHIDA, CONNOR ANDREW · 2021 to 2022
$77k
NCI NIH HHS R35 CA209919NHGRI NIH HHS P50 HG007735NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS F31 HL156468NIAID NIH HHS R01 AI136972NIAID NIH HHS U01 AI142817NIAMS NIH HHS P30 AR070155NIAMS NIH HHS R01 AR071522NIGMS NIH HHS R01 GM065050
6 · The paper itself

Abstract

CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome remains a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that chromosome loss was generalizable across the genome and resulted in partial and entire loss of the chromosome, including in pre-clinical chimeric antigen receptor T cells. T cells with chromosome loss persisted for weeks in culture, implying the potential to interfere with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells,

Identifiers

PMID36993359
PMCPMC10055432
OpenAlexW4353031791

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.