Evidence map›Paper›PMID 40967220›Full record

ArticleCell reports. Medicine2025

Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells.

Eva E R Segura, Kevyn Hart, Beatriz Campo Fernandez, Devin Brown, Kevin Tam, Andrea Gutierrez Garcia, Eva Seigneurbieux, Karen Li, Carol Mulumba, Emma Blakely and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Eva E R SeguraMolecular Biology Interdepartmental Doctoral Program, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: evarosesegura@ucla.edu.
Kevyn HartDepartment of Human Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Beatriz Campo FernandezDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Devin BrownDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Kevin TamDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Andrea Gutierrez GarciaDepartment of Biology at California State University, Northridge, Northridge, CA 91330, USA.
Eva SeigneurbieuxDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karen LiDepartment of Molecular, Cell, and Developmental Biology at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Carol MulumbaDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Emma BlakelyDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Katelyn MasiukDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Roshani SinhaDepartment of Surgery, Division of Pediatric Surgery at University of California, San Francisco, San Francisco, CA 94143, USA.
Devesh SharmaDepartment of Surgery, Division of Pediatric Surgery at University of California, San Francisco, San Francisco, CA 94143, USA.
John EverettDepartment of Microbiology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
Matthew HogenauerDepartment of Microbiology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
M Kyle CromerDepartment of Surgery, Division of Pediatric Surgery at University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at University of California, San Francisco, San Francisco, CA 94143, USA; Center for Maternal-Fetal Precision Medicine at University of California, San Francisco, San Francisco, CA 94143, USA.
Frederic BushmanDepartment of Microbiology, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA.
Tippi C MacKenzieDepartment of Surgery, Division of Pediatric Surgery at University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at University of California, San Francisco, San Francisco, CA 94143, USA; Center for Maternal-Fetal Precision Medicine at University of California, San Francisco, San Francisco, CA 94143, USA.
Donald B KohnDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics (Hematology/Oncology), David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dkohn1@mednet.ucla.edu.

Funding

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
NHLBI NIH HHS R01 HL161291
6 · The paper itself

Abstract

Alpha thalassemia major (ATM) is an inherited blood disorder caused by the absence of all four α-globin genes (HBA2/1), resulting in severe anemia and lifelong transfusion dependence. While allogeneic hematopoietic stem cell transplantation (HSCT) offers a potential cure, donor availability remains limited. We present a gene therapy approach for autologous HSCT using lentiviral vectors (LVs) to deliver HBA2 under the regulation of optimized β-globin locus control region (LCR) enhancers, restoring α-globin expression in red blood cells. The best-performing LVs, erythroid vector-alpha (EV-α) and EV-α-UV, achieved up to 100% transduction efficiency in human hematopoietic stem and progenitor cells (HSPCs), optimal vector copy numbers, and safe integration profiles. ATM-derived HSPCs from three donors treated with these LVs yielded α/β-globin mRNA and chain ratios within the therapeutic range (∼0.5+), and restored hemoglobin levels by 50%-100%. These findings establish the safety and clinical potential of EV-α and EV-α-UV as a promising autologous stem cell gene therapy for ATM.

Indexed as

alpha-Globinsalpha-ThalassemiaErythrocytesGenetic TherapyGenetic VectorsHematopoietic Stem CellsHematopoietic Stem Cell TransplantationLentivirusbeta-GlobinsHumansalpha-Globinsbeta-Globinsalpha globinalpha thalassemia majoranemiaautologousbeta-globin LCRgene therapyhematopoietic stem cellhemoglobin levellentiviral vectorsred blood cells

Identifiers

PMID40967220
PMCPMC12629793

What OpenQuestion holds

Textmetadata
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.