Evidence map›Paper›PMID 23534873›Full record

ArticleHuman gene therapy2013

Kinetics of adeno-associated virus serotype 2 (AAV2) and AAV8 capsid antigen presentation in vivo are identical.

Yi He, Marc S Weinberg, Matt Hirsch, Mark C Johnson, Roland Tisch, R Jude Samulski, Chengwen Li

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Application of polyploid adeno-associated virus vectors for transduction enhancement and neutralizing antibody evasion.Journal of controlled release : official journal of the Controlled Release Society · 2017
    Article
  17. Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2016
    Article
  18. Review
  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

7 authors at 2 institutions in 2 countries.

Yi HeInstitute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.
Marc S Weinberg
Matt Hirsch
Mark C Johnson
Roland Tisch
R Jude Samulski
Chengwen Li
University of North Carolina at Chapel Hill · USChinese Academy of Medical Sciences & Peking Union Medical College · CN

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Training & EducationU54AR056953 · NIAMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 2008 to 2012
$7.1M
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
CTL response to AAV VectorR01AI080726 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LI, CHENGWEN, SAMULSKI, RICHARD J · 2010 to 2014
$1.8M
Reversal of Type I Diabetes in NOD MiceR01DK081585 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TISCH, ROLAND M · 2009 to 2012
$1.2M
Galanin, Seizures, and NeuroinflammationF32NS070356 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WEINBERG, MARC SCOTT · 2011 to 2013
$166k
NCI NIH HHS P30 CA016086NCI NIH HHS P30CA06086NIAID NIH HHS 1R01AI080726NIAID NIH HHS 5R01AI072176NIAID NIH HHS R01 AI080726NIAMS NIH HHS 5U54AR056953NIDDK NIH HHS 5R01DK081585NIDDK NIH HHS 5R01DK084033NIDDK NIH HHS R01 DK084033NINDS NIH HHS F32NS070356
6 · The paper itself

Abstract

Adeno-associated viral (AAV) vectors 2 and 8 have been used in clinical trials for patients with hemophilia, and data suggest that the capsid-specific CD8⁺ T cell response has had a negative impact on therapeutic success. To date the pattern of capsid cross-presentation from AAV2 and AAV8 transduction in vivo has not been elucidated. Previously, we have demonstrated that an engineered AAV2 virus carrying the immune-dominant SIINFEKL peptide in the capsid backbone was indistinguishable from wild type with respect to titer, tropism, and the ability to induce capsid-specific CD8⁺ T cell responses in vivo. In this study, we used the same strategy to engineer an AAV8 vector and demonstrated that antigen from SIINFEKL peptide-integrated AAV8 capsid was effectively presented via either plasmid transfection or AAV8 transduction in vitro. The tissue tropism and transgene expression kinetics of the engineered AAV8 vector in vivo were identical to that of wild-type AAV8. Animal studies show that capsid antigen presentation from AAV transduction was dose dependent, and more importantly, the proliferation of capsid-specific CD8⁺ T cells had similar kinetics (detectable before 30 days and undetectable after 40 days) for both AAV2 and AAV8 vectors. Elucidation of the kinetics of capsid antigen presentation from AAV transduction by various serotypes provides new insight into the potential impact CD8⁺ T cells can have during clinical trials and may help with rational design of effective strategies to prevent capsid-specific CD8⁺ T cell-mediated elimination of AAV-transduced target cells.

Indexed as

AnimalsAntigen PresentationCapsid ProteinsCell LineClinical Trials as TopicCross-PrimingDependovirusGenetic VectorsHumansKineticsMaleSerotypingTransduction, GeneticCapsid Proteins

Identifiers

PMID23534873
PMCPMC3655625
OpenAlexW2071085324

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.