Evidence map›Paper›PMID 39754719›Full record

ArticleCell reports2025

Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.

Simon N Chu, Eric Soupene, Devesh Sharma, Roshani Sinha, Travis McCreary, Britney Hernandez, Huifeng Shen, Beeke Wienert, Chance Bowman, Han Yin and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026
    Review
  2. Article
  3. Article
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  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Simon N ChuDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Eric SoupeneDepartment of Pediatrics, University of California, San Francisco, Oakland, CA 94609, USA.
Devesh SharmaDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Roshani SinhaDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Travis McCrearyDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Britney HernandezAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Huifeng ShenAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Beeke WienertGladstone Institutes, San Francisco, CA 94158, USA.
Chance BowmanDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Han YinDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Benjamin J LeschDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Kun JiaDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Kathleen A RomeroAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Zachary KostamoAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Yankai ZhangAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Tammy TranDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Marco CorderoDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Shota HommaDepartment of Genetics, Stanford University, Stanford, CA 94305, USA.
Jessica P HamptonDepartment of Pediatrics, Stanford University, Stanford, CA 94305, USA.
James M GardnerDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Bruce R ConklinGladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA.
Tippi C MacKenzieDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Vivien A SheehanAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA 30329, USA.
Matthew H PorteusDepartment of Pediatrics, Stanford University, Stanford, CA 94305, USA.
M Kyle CromerDepartment of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli & Edythe Broad Center for Regeneration Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: kyle.cromer@uscf.edu.

Funding

Project 3: Control of cardiac transcription by MEF2 and myocardinP01HL146366 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI SRIVASTAVA, DEEPAK · 2019 to 2023
$13.7M
Developing genome editing strategies to treat alpha thalassemiaR01HL161291 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Michael Kyle Cromer, Tippi Mackenzie · 2022 to 2026
$3.6M
Filling a Void of Research (FAVOR) Training for Transplant SurgeonsT32AI125222 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PETER G STOCK, Minnie M Sarwal · 2016 to 2026
$3.4M
Protein quality control, cardiomyopathy, cardiotoxicity and human isogenic iPSCsR01HL135358 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2017 to 2020
$2.0M
Identifying Therapeutic Targets for RNA Splicing-Related CardiomyopathyR01HL130533 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2016 to 2019
$1.8M
C9orf72 frontotemporal dementia (FTD) and amyotrophic lateral sclerosis(ALS): using patient cells and CRISPR to reveal therapeutic approachesR01AG072052 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2024 to 2025
$1.4M
NHLBI NIH HHS P01 HL146366NHLBI NIH HHS R01 HL130533NHLBI NIH HHS R01 HL135358NHLBI NIH HHS R01 HL161291NIAID NIH HHS T32 AI125222NIA NIH HHS R01 AG072052
6 · The paper itself

Abstract

The most severe form of α-thalassemia results from loss of all four copies of α-globin. Postnatally, patients face challenges similar to β-thalassemia, including severe anemia and erythrotoxicity due to the imbalance of β-globin and α-globin chains. Despite progress in genome editing treatments for β-thalassemia, there is no analogous curative option for α-thalassemia. To address this, we designed a Cas9/AAV6-mediated genome editing strategy that integrates a functional α-globin gene into the β-globin locus in α-thalassemia patient-derived hematopoietic stem and progenitor cells (HSPCs). Incorporation of a truncated erythropoietin receptor transgene into the α-globin integration cassette significantly increased erythropoietic output from edited HSPCs and led to the most robust production of α-globin, and consequently hemoglobin tetramers. By directing edited HSPCs toward increased production of clinically relevant erythroid cells, this approach has the potential to mitigate the limitations of current treatments for the hemoglobinopathies, including low genome editing and low engraftment rates.

Indexed as

alpha-Globinsalpha-ThalassemiaErythroid CellsHemoglobinsReceptors, Erythropoietinbeta-GlobinsCRISPR-Cas SystemsErythropoiesisGene EditingGene Knock-In TechniquesHematopoietic Stem CellsHumansalpha-Globinsbeta-GlobinsHemoglobinsReceptors, Erythropoietinadeno-associated virusCP: Stem cell researchCRISPRgenome editinghematopoietic stem and progenitor cellshemoglobinred blood cellsRNA sequencingα-thalassemia

Identifiers

PMID39754719
PMCPMC11837859

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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.