Evidence map›Paper›PMID 39414860›Full record

Trial reportScientific reports2024

Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.

Samuel Lessard, Pauline Rimmelé, Hui Ling, Kevin Moran, Benjamin Vieira, Yi-Dong Lin, Gaurav Manohar Rajani, Vu Hong, Andreas Reik, Richard Boismenu and 18 more

Abstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing 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

14 citing papers in PubMed.

  1. Review
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  12. Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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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

28 authors.

Samuel Lessard *Rare Blood Disorders, Sanofi, Waltham, MA, 02451, USA. samuel.lessard@sanofi.com.
Pauline Rimmelé *Rare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Hui LingRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Kevin MoranRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Benjamin VieiraRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Yi-Dong LinRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Gaurav Manohar RajaniRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Vu HongRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Andreas ReikSangamo Therapeutics, Richmond, CA, 94804, USA.
Richard BoismenuSangamo Therapeutics, Richmond, CA, 94804, USA.
Ben HsuSangamo Therapeutics, Richmond, CA, 94804, USA.
Michael ChenSangamo Therapeutics, Richmond, CA, 94804, USA.
Bettina M CockroftSangamo Therapeutics, Richmond, CA, 94804, USA.
Naoya UchidaCellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institutes/National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, National Institutes of Health (NIH), Bethesda, MD, USA.
John TisdaleCellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institutes/National Institute of Diabetes and Digestive and Kidney Diseases, National Heart, National Institutes of Health (NIH), Bethesda, MD, USA.
Asif AlaviHenry Ford Cancer Institute, Detroit, MI, USA.
Lakshmanan KrishnamurtiEmory University, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Mehrdad AbediUniversity of California-Davis Medical Center, Sacramento, CA, USA.
Isobelle GaleonRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
David ReinerRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Lin WangRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Anne RameziRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Pablo RendoRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Mark C WaltersUniversity of California San Francisco Benioff Children's Hospital, Oakland, CA, USA.
Dana LevasseurRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Robert PetersRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Timothy HarrisRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.
Alexandra HicksRare Blood Disorders, Sanofi, Waltham, MA, 02451, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

Indexed as

Anemia, Sickle CellFetal HemoglobinGene EditingHematopoietic Stem CellsZinc Finger NucleasesAdultAnimalsFemaleHematopoietic Stem Cell TransplantationHumansMaleMiceRepressor ProteinsBCL11A protein, humanFetal HemoglobinRepressor ProteinsZinc Finger Nucleases

Identifiers

PMID39414860
PMCPMC11484757

What OpenQuestion holds

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Registered trials

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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.