Evidence map›Paper›PMID 31628051›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small β-Globin Locus Control Region Elements.

Richard A Morgan, Mildred J Unti, Bamidele Aleshe, Devin Brown, Kyle S Osborne, Colin Koziol, Paul G Ayoub, Oliver B Smith, Rachel O'Brien, Curtis Tam and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Review
  2. Article
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  5. Review
  6. Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  7. A differentiated β-globin gene replacement strategy uses heterologous introns to restore physiological expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
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  16. Article
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  18. Article
  19. Development and clinical translation ofComputational and structural biotechnology journal · 2022
    Review
  20. Review
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

16 authors.

Richard A MorganCharles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mildred J UntiDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bamidele AlesheDepartment 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.
Kyle S OsborneDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Colin KoziolDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Paul G AyoubDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Oliver B SmithDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Rachel O'BrienDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Curtis TamDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Eric MiyahiraDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Marlene RuizDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jason P QuintosCSUN-UCLA Stem Cell Scientist Training Program, California State University, Northridge, Northridge, CA 91330, USA.
Shantha SenadheeraDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Roger P HollisDepartment of Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Donald B KohnDepartment of Molecular and Medical Pharmacology, 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; Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA; The Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: dkohn1@mednet.ucla.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
MARC U*STAR Program at the University of California, Los AngelesT34GM008563 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MCEVOY, MEGAN M, POE, GINA R · 1996 to 2023
$9.7M
Improved Globin Expression Vectors for Gene Therapy of Human HemoglobinopathiesF31HL134313 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MORGAN, RICHARD A · 2016 to 2020
$211k
NHLBI NIH HHS F31 HL134313NIGMS NIH HHS T32 GM008042NIGMS NIH HHS T34 GM008563
6 · The paper itself

Abstract

β-globin lentiviral vectors (β-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of preserving efficacious expression while increasing vector performance, we used published genomic and epigenomic data available through ENCODE to redefine enhancer element boundaries of the β-globin locus control region (LCR) to construct novel ENCODE core sequences. These novel LCR elements were used to design a β-LV of reduced proviral length, termed CoreGA-AS3-FB, produced at higher titers and possessing superior gene transfer to HSPCs when compared to the full-length parental β-LV at equal MOI. At low vector copy number, vectors containing the ENCODE core sequences were capable of reversing the sickle phenotype in a mouse model of SCD. These studies provide a β-LV that will be beneficial for gene therapy of SCD by significantly reducing the cost of vector production and extending the vector supply.

Indexed as

Genetic VectorsAnemia, Sickle CellAnimalsbeta-GlobinsBone Marrow CellsDisease Models, AnimalGenetic TherapyHealthy VolunteersHEK293 CellsHematopoietic Stem CellsHumansLentivirusLocus Control RegionMicePhenotypeTransduction, Geneticbeta-GlobinsENCODEgene therapyhematopoietic stem cellhemoglobinopathieslentiviral vectorlocus control regionsickle cell diseasetransplantation

Identifiers

PMID31628051
PMCPMC6953778

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.