Evidence map›Paper›PMID 31178391›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019

Editing the Sickle Cell Disease Mutation in Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates.

Zulema Romero, Anastasia Lomova, Suzanne Said, Alexandra Miggelbrink, Caroline Y Kuo, Beatriz Campo-Fernandez, Megan D Hoban, Katelyn E Masiuk, Danielle N Clark, Joseph Long and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

90 citing papers in PubMed, 123 citations in OpenAlex.

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  19. Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
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30 more citing papers are in PubMed but not listed here.

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 at 1 institution in 1 country.

Zulema RomeroDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Anastasia LomovaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Suzanne SaidDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Alexandra MiggelbrinkDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Caroline Y KuoDivision of Allergy & Immunology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA, USA.
Beatriz Campo-FernandezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Megan D HobanDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Katelyn E MasiukDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Danielle N ClarkDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Joseph LongDivision of Allergy & Immunology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA, USA.
Julie M SanchezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Miriam VelezDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Eric MiyahiraDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Ruixue ZhangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Devin BrownDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Xiaoyan WangDepartment of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, CA, USA.
Yerbol Z KurmangaliyevDepartment of Biological Chemistry, HHMI, University of California, Los Angeles, Los Angeles, CA, USA.
Roger P HollisDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Donald B KohnDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: dkohn1@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

UCLA MSD ProgramR25GM055052 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BARBER, PAUL HENRY, HASSON, TAMA W. · 1996 to 2021
$9.2M
NIGMS NIH HHS R25 GM055052
6 · The paper itself

Abstract

Site-specific correction of a point mutation causing a monogenic disease in autologous hematopoietic stem and progenitor cells (HSPCs) can be used as a treatment of inherited disorders of the blood cells. Sickle cell disease (SCD) is an ideal model to investigate the potential use of gene editing to transvert a single point mutation at the β-globin locus (HBB). We compared the activity of zinc-finger nucleases (ZFNs) and CRISPR/Cas9 for editing, and homologous donor templates delivered as single-stranded oligodeoxynucleotides (ssODNs), adeno-associated virus serotype 6 (AAV6), integrase-deficient lentiviral vectors (IDLVs), and adenovirus 5/35 serotype (Ad5/35) to transvert the base pair responsible for SCD in HBB in primary human CD34+ HSPCs. We found that the ZFNs and Cas9 directed similar frequencies of nuclease activity. In vitro, AAV6 led to the highest frequencies of homology-directed repair (HDR), but levels of base pair transversions were significantly reduced when analyzing cells in vivo in immunodeficient mouse xenografts, with similar frequencies achieved with either AAV6 or ssODNs. AAV6 also caused significant impairment of colony-forming progenitors and human cell engraftment. Gene correction in engrafting hematopoietic stem cells may be limited by the capacity of the cells to mediate HDR, suggesting additional manipulations may be needed for high-efficiency gene correction in HSPCs.

Indexed as

Gene EditingMutationAnemia, Sickle Cellbeta-GlobinsCRISPR-Cas SystemsDependovirusEndonucleasesGene ExpressionGene TargetingGenetic TherapyGenetic VectorsHematopoietic Stem CellsHumansParvovirinaeTissue DonorsTransduction, Geneticbeta-GlobinsEndonucleasesZinc Finger Nucleasesadeno-associated virus 6CRISPR/Cas9gene editinghematopoietic stem cellshomologous recombinationnon-homologous end joiningsickle cell diseasezinc finger nuclease

Identifiers

PMID31178391
PMCPMC6697408
OpenAlexW2946205118

What OpenQuestion holds

Textmetadata
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.