Evidence map›Paper›PMID 24917028›Full record

ArticleBiomaterials2014

Naturally enveloped AAV vectors for shielding neutralizing antibodies and robust gene delivery in vivo.

Bence György, Zachary Fitzpatrick, Matheus H W Crommentuijn, Dakai Mu, Casey A Maguire

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

105 citing papers in PubMed, 147 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Gene therapy for atrial fibrillation.Journal of molecular and cellular cardiology · 2024
    Review
  19. Review
  20. Article

45 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

5 authors at 4 institutions in 2 countries.

Bence GyörgyDepartment of Neurology, The Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, USA.
Zachary FitzpatrickDepartment of Neurology, The Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, USA; Louisiana State University, Baton Rouge, LA, USA.
Matheus H W CrommentuijnDepartment of Neurology, The Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, USA; Neuro-oncology Research Group, Department of Neurosurgery, Cancer Center Amsterdam, and VU University Medical Center, Amsterdam, The Netherlands.
Dakai MuDepartment of Neurology, The Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, USA.
Casey A MaguireDepartment of Neurology, The Massachusetts General Hospital and Neuroscience Program, Harvard Medical School, Boston, USA. Electronic address: cmaguire@mgh.harvard.edu.
Massachusetts General Hospital · USAmsterdam UMC Location VUmc · NLHarvard University · USLouisiana State University · US

Funding

Interdepartmental Neuroscience CenterP30NS045776 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, TANNOUS, BAKHOS A · 2003 to 2018
$11.1M
MOLECULAR BASIS OF INHERITED DEAFNESSR01DC002281 · NIDCD · MASSACHUSETTS GENERAL HOSPITAL · PI COREY, DAVID P · 1994 to 2018
$4.4M
A hybrid microvesicle/virus vector for targeted gene transfer to the brainR21NS081374 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI MAGUIRE, CASEY A · 2012 to 2013
$449k
NIDCD NIH HHS R01 DC002281NIDCD NIH HHS R01DC02281NINDS NIH HHS P30 NS045776NINDS NIH HHS R21 NS081374NINDS NIH HHS R21 NS081374-01
6 · The paper itself

Abstract

Recently adeno-associated virus (AAV) became the first clinically approved gene therapy product in the western world. To develop AAV for future clinical application in a widespread patient base, particularly in therapies which require intravenous (i.v.) administration of vector, the virus must be able to evade pre-existing antibodies to the wild type virus. Here we demonstrate that in mice, AAV vectors associated with extracellular vesicles (EVs) can evade human anti-AAV neutralizing antibodies. We observed different antibody evasion and gene transfer abilities with populations of EVs isolated by different centrifugal forces. EV-associated AAV vector (ev-AAV) was up to 136-fold more resistant over a range of neutralizing antibody concentrations relative to standard AAV vector in vitro. Importantly in mice, at a concentration of passively transferred human antibodies which decreased i.v. administered standard AAV transduction of brain by 80%, transduction of ev-AAV transduction was not reduced and was 4000-fold higher. Finally, we show that expressing a brain targeting peptide on the EV surface allowed significant enhancement of transduction compared to untargeted ev-AAV. Using ev-AAV represents an effective, clinically relevant approach to evade human neutralizing anti-AAV antibodies after systemic administration of vector.

Indexed as

AnimalsAntibodies, NeutralizingCell LineDependovirusFemaleGenetic TherapyGenetic VectorsGene Transfer TechniquesHumansMiceMice, NudeTransduction, GeneticAntibodies, NeutralizingAdeno-associated virusExosomesExtracellular vesiclesGene deliveryGene therapyMicrovesicles

Identifiers

PMID24917028
PMCPMC4104587
OpenAlexW2006920577

What OpenQuestion holds

Textmetadata
LicenceTDM
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.