Evidence map›Paper›PMID 27834949›Full record

ArticleGene therapy2017

Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications.

M Wang, J Sun, A Crosby, K Woodard, M L Hirsch, R J Samulski, C Li

Abstract read
In one paragraph

Article in Gene therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 52 citations in OpenAlex.

  1. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  8. AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. Re-administration of AAV vectors by masking with host albumin: A Goldilocks hypothesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Observational
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

7 authors at 2 institutions in 2 countries.

M WangStem Cell Transplantation Center, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin, China.
J SunGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
A CrosbyGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
K WoodardGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
M L HirschGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
R J SamulskiGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
C LiGene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
University of North Carolina at Chapel Hill · USCommunities In Schools of Orange County · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
Translational Nanosystems for Improved Lung Cancer Treatment with Small MoleculesU54CA151652 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HAROON, ZISHAN A, TEPPER, JOEL E · 2010 to 2014
$12.1M
VECTOR AND MOLECULAR BIOLOGY COREP01HL112761 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI MONAHAN, PAUL E · 2013 to 2017
$11.3M
Rational and Combinatorial Engineering of AAV VectorsR01AI072176 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI HIRSCH, MATTHEW LOUIS, SAMULSKI, RICHARD J · 2008 to 2017
$3.7M
AAV Gene Therapy for AAT DeficiencyR01DK084033 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, CHENGWEN · 2009 to 2016
$2.2M
Enhance AAV Liver Transduction with Capsid Immune EvasionR01AI117408 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, CHENGWEN, SAMULSKI, RICHARD J · 2016 to 2020
$2.0M
Directed evolution of AAV vectors for hemophilia to evade neutralizationR01HL125749 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, CHENGWEN, NICHOLS, TIMOTHY CHARLES · 2015 to 2018
$1.5M
NCI NIH HHS P30 CA016086NCI NIH HHS U54 CA151652NHLBI NIH HHS P01 HL112761NHLBI NIH HHS R01 HL125749NIAID NIH HHS R01 AI072176NIAID NIH HHS R01 AI117408NIDDK NIH HHS R01 DK084033
6 · The paper itself

Abstract

Recent hemophilia B clinical trials using adeno-associated virus (AAV) gene delivery have demonstrated much lower coagulation factor IX (FIX) production in patients compared with the high levels observed in animal models and AAV capsid-specific cytotoxic T lymphocyte response elicited at high doses of AAV vectors. These results emphasize the necessity to explore effective approaches for enhancement of AAV transduction. Initially, we found that incubation of all AAV vectors with human serum enhanced AAV transduction. Complementary analytical experiments demonstrated that human serum albumin (HSA) directly interacted with the AAV capsid and augmented AAV transduction. The enhanced transduction was observed with clinical grade HSA. Mechanistic studies suggest that HSA increases AAV binding to target cells, and that the interaction of HSA with AAV does not interfere with the AAV infection pathway. Importantly, HSA incubation during vector dialysis also increased transduction. Finally, HSA enhancement of AAV transduction in a model of hemophilia B displayed greater than a fivefold increase in vector-derived circulating FIX, which improved the bleeding phenotype correction. In conclusion, incubation of HSA with AAV vectors supports a universal augmentation of AAV transduction and, more importantly, this approach can be immediately transitioned to the clinic for the treatment of hemophilia and other diseases.

Indexed as

AnimalsCapsidCell Line, TumorDependovirusGenetic TherapyGene Transfer TechniquesHEK293 CellsHemophilia BHumansMiceMice, Inbred C57BLProtein BindingSerum AlbuminSerum Albumin

Identifiers

PMID27834949
PMCPMC5269444
OpenAlexW2554064291

What OpenQuestion holds

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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.