Evidence map›Paper›PMID 32276210›Full record

ArticleMolecular therapy. Nucleic acids2020

Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.

Hua Yang, Keyun Qing, Geoffrey D Keeler, Ling Yin, Mario Mietzsch, Chen Ling, Brad E Hoffman, Mavis Agbandje-McKenna, Mengqun Tan, Wei Wang and 1 more

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

Article in Molecular therapy. Nucleic acids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Human Hepatocyte Transduction with Adeno-Associated Virus Vector.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021
    Review
  16. Role of Essential Metal Ions in AAV Vector-Mediated Transduction.Molecular therapy. Methods & clinical development · 2020
    Article
  17. 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

11 authors at 3 institutions in 2 countries.

Hua YangDepartment of Radiology, Institute of Cell and Gene Therapy, The Third Xiangya Hospital, Central South University, Changsha, China; Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
Keyun QingDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
Geoffrey D KeelerDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
Ling YinDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Mario MietzschPowell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, USA.
Chen LingState Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Brad E HoffmanDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA.
Mavis Agbandje-McKennaPowell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, USA.
Mengqun TanDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
Wei WangDepartment of Radiology, Institute of Cell and Gene Therapy, The Third Xiangya Hospital, Central South University, Changsha, China. Electronic address: cjr.wangwei@vip.163.com.
Arun SrivastavaDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: aruns@peds.ufl.edu.
University of Florida · USCentral South University · CNFudan University · CN

Funding

Structural studies of AAV capsids and their glycan receptor interactionsR01GM082946 · NIGMS · UNIVERSITY OF FLORIDA · PI ROBERT MCKENNA · 2007 to 2026
$6.1M
Next Generation of Recombinant AAV Serotype Vectors for Gene TherapyR01HL097088 · NHLBI · UNIVERSITY OF FLORIDA · PI GAO, GUANGPING, HERZOG, ROLAND W. · 2010 to 2018
$5.4M
Mechanism of high-efficiency transduction of hepatocytes by optimized AAV vectorsR01GM119186 · NIGMS · UNIVERSITY OF FLORIDA · PI ASLANIDI, GEORGE V, SRIVASTAVA, ARUN · 2017 to 2021
$1.5M
Safety and efficacy of optimized AAV3 vectors in murine and NHP liversR21EB015684 · NIBIB · UNIVERSITY OF FLORIDA · PI GAO, GUANGPING, SRIVASTAVA, ARUN · 2012 to 2013
$432k
AAV2 and hepatocellular carcinomaR21AI131328 · NIAID · UNIVERSITY OF FLORIDA · PI SRIVASTAVA, ARUN · 2017 to 2018
$408k
Development of Optimized AAV Serotype Vectors for Human Gene TherapyR41AI122735 · NIAID · MEDOSOME BIOTEC, LLC · PI SRIVASTAVA, ARUN · 2016 to 2016
$294k
NHLBI NIH HHS R01 HL097088NIAID NIH HHS R21 AI131328NIAID NIH HHS R41 AI122735NIBIB NIH HHS R21 EB015684NIGMS NIH HHS R01 GM082946NIGMS NIH HHS R01 GM119186
6 · The paper itself

Abstract

We have reported that of the 10 most commonly used adeno-associated virus (AAV) serotype vectors, AAV6 is the most efficient in transducing primary human hematopoietic stem cells (HSCs) in vitro, as well as in vivo. More recently, polyvinyl alcohol (PVA), was reported to be a superior replacement for human serum albumin (HSA) for ex vivo expansion of HSCs. Since HSA has been shown to increase the transduction efficiency of AAV serotype vectors, we evaluated whether PVA could also enhance the transduction efficiency of AAV6 vectors in primary human HSCs. We report here that up to 12-fold enhancement in the transduction efficiency of AAV6 vectors can be achieved in primary human HSCs with PVA. We also demonstrate that the improvement in the transduction efficiency is due to PVA-mediated improved entry and intracellular trafficking of AAV6 vectors in human hematopoietic cells in vitro, as well as in murine hepatocytes in vivo. Taken together, our studies suggest that the use of PVA is an attractive strategy to further improve the efficacy of AAV6 vectors. This has important implications in the optimal use of these vectors in the potential gene therapy and genome editing for human hemoglobinopathies such as β-thalassemia and sickle cell disease.

Indexed as

AAV vectorsgene transfergenome editinghematopoietic stem cellshemoglobinopathies

Identifiers

PMID32276210
PMCPMC7150427
OpenAlexW3013132128

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.