Evidence map›Paper›PMID 25355884›Full record

ArticleJournal of virology2015

Enhanced transgene expression from recombinant single-stranded D-sequence-substituted adeno-associated virus vectors in human cell lines in vitro and in murine hepatocytes in vivo.

Chen Ling, Yuan Wang, Yuan Lu, Lina Wang, Giridhara R Jayandharan, George V Aslanidi, Baozheng Li, Binbin Cheng, Wenqin Ma, Thomas Lentz and 5 more

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

Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.0field-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

32 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Review
  3. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  11. Article
  12. Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022
    Review
  13. Reply to "D" matters in recombinant AAV packaging.Molecular therapy : the journal of the American Society of Gene Therapy · 2021
    Article
  14. Article
  15. Article
  16. Article
  17. Role of Essential Metal Ions in AAV Vector-Mediated Transduction.Molecular therapy. Methods & clinical development · 2020
    Article
  18. Article
  19. Article
  20. 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

15 authors at 7 institutions in 3 countries.

Chen LingDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA lingchen@peds.ufl.edu aruns@peds.ufl.edu.
Yuan WangDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Yuan LuDepartment of Orthopedics & Rehabilitative Medicine, University of Florida College of Medicine, Gainesville, Florida, USA.
Lina WangDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
Giridhara R JayandharanDepartment of Haematology and Centre for Stem Cell Research, Christian Medical College, Vellore, India.
George V AslanidiDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA.
Baozheng LiDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA.
Binbin ChengDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
Wenqin MaDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA.
Thomas LentzGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Changquan LingDepartment of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Xiao XiaoGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Division of Molecular Pharmaceutics, University of North Carolina School of Pharmacy, Chapel Hill, North Carolina, USA.
R Jude SamulskiGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Nicholas MuzyczkaPowell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA Genetics Institute, University of Florida College of Medicine, Gainesville, Florida, USA.
Arun SrivastavaDivision of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, USA Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, Florida, USA Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, Florida, USA Genetics Institute, University of Florida College of Medicine, Gainesville, Florida, USA Shands Cancer Center, University of Florida College of Medicine, Gainesville, Florida, USA lingchen@peds.ufl.edu aruns@peds.ufl.edu.
Florida College · USUniversity of Florida · USUniversity of North Carolina at Chapel Hill · USChristian Medical College & Hospital · INSecond Military Medical University · CNShanghai University of Traditional Chinese Medicine · CNUniversity of Florida Health · US

Funding

UF Clinical and Translational Science AwardUL1TR000064 · NCATS · UNIVERSITY OF FLORIDA · PI NELSON, DAVID R · 2012 to 2014
$12.2M
Strategies for Sustained Effect of AAV-mediated Correction of Pompe DiseaseP01DK058327 · NIDDK · UNIVERSITY OF FLORIDA · PI CAMPBELL-THOMPSON, MARTHA · 2000 to 2009
$11.0M
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
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
NCATS NIH HHS UL1 TR000064NHLBI NIH HHS R01 HL-097088NHLBI NIH HHS R01 HL097088NIBIB NIH HHS R21 EB-015684NIBIB NIH HHS R21 EB015684NIDDK NIH HHS P01 DK-058327NIDDK NIH HHS P01 DK058327
6 · The paper itself

Abstract

unlabelledWe have previously reported that the removal of a 20-nucleotide sequence, termed the D sequence, from both ends of the inverted terminal repeats (ITRs) in the adeno-associated virus serotype 2 (AAV2) genome significantly impairs rescue, replication, and encapsidation of the viral genomes (X. S. Wang, S. Ponnazhagan, and A. Srivastava, J Mol Biol 250:573-580, 1995; X. S. Wang, S. Ponnazhagan, and A. Srivastava, J Virol 70:1668-1677, 1996). Here we describe that replacement of only one D sequence in either ITR restores each of these functions, but DNA strands of only single polarity are encapsidated in mature progeny virions. Since most commonly used recombinant AAV vectors contain a single-stranded DNA (ssDNA), which is transcriptionally inactive, efficient transgene expression from AAV vectors is dependent upon viral second-strand DNA synthesis. We have also identified a transcription suppressor sequence in one of the D sequences, which shares homology with the binding site for the cellular NF-κB-repressing factor (NRF). The removal of this D sequence from, and replacement with a sequence containing putative binding sites for transcription factors in, single-stranded AAV (ssAAV) vectors significantly augments transgene expression both in human cell lines in vitro and in murine hepatocytes in vivo. The development of these genome-modified ssAAV vectors has implications not only for the basic biology of AAV but also for the optimal use of these vectors in human gene therapy. IMPORTANCE: The results of the studies described here not only have provided novel insights into some of the critical steps in the life cycle of a human virus, the adeno-associated virus (AAV), that causes no known disease but have also led to the development of novel recombinant AAV vectors which are more efficient in allowing increased levels of gene expression. Thus, these studies have significant implications for the potential use of these novel AAV vectors in human gene therapy.

Indexed as

Gene ExpressionGenetic VectorsTransgenesAnimalsCell LineDependovirusGenetic TherapyHepatocytesHumansMaleMice, Inbred C57BLSequence DeletionVirus Assembly

Identifiers

PMID25355884
PMCPMC4300666
OpenAlexW1978052389

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.