Evidence map›Paper›PMID 28926997›Full record

ArticleGenes2017

Effects of Cellular Methylation on Transgene Expression and Site-Specific Integration of Adeno-Associated Virus.

Diptiman Chanda, Jonathan A Hensel, Jerome T Higgs, Rajat Grover, Niroop Kaza, Selvarangan Ponnazhagan

Open access · goldAbstract read
In one paragraph

Article in Genes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 19% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Artificial Intelligence-Based Approaches for AAV Vector Engineering.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  8. Article
  9. Targeted long-read sequencing captures CRISPR editing and AAV integration outcomes in brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  10. Article
  11. Viral vector platforms within the gene therapy landscape.Signal transduction and targeted therapy · 2021
    Review
  12. Condensed Tannins in White Clover (Frontiers in plant science · 2021
    Article
  13. Article
  14. Article
  15. Article
  16. 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

6 authors at 1 institution in 1 country.

Diptiman ChandaDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. diptimanchanda@uabmc.edu.
Jonathan A HenselDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jonathanhensel@uabmc.edu.
Jerome T HiggsDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. jthiggs@uab.edu.
Rajat GroverDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. grover@uab.edu.
Niroop KazaDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. kaza@uab.edu.
Selvarangan PonnazhaganDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. pons@uab.edu.
University of Alabama at Birmingham · US

Funding

Targeted therapy for breast cancer with osteolytic bone damageR01CA184770 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2015 to 2019
$1.7M
Targeted Stem Cell Therapy Coupling Angiogenesis and Osteogenesis for Bone DefectR01AR060948 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2011 to 2016
$1.6M
rAAV vaccine vectorR01CA132077 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2008 to 2012
$1.5M
Gene-Engineered and Targeted Stem Cell Therapy for MyelomaR01CA133737 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI PONNAZHAGAN, SELVARANGAN · 2009 to 2013
$1.5M
NCI NIH HHS R01 CA132077NCI NIH HHS R01 CA133737NCI NIH HHS R01 CA184770NIAMS NIH HHS R01 AR060948
6 · The paper itself

Abstract

DNA methylation is a major epigenetic event that affects not only cellular gene expression but that also has the potential to influence bacterial and viral DNA in their host-dependent functions. Adeno-associated virus (AAV) genome contains a high degree of CpG sequences capable of methylation in its terminal repeat sequences, which are the sole elements retained in AAV-based vectors used in gene therapy. The present study determined the influence of methylation status of the host cell on wild type (wt) AAV integration and recombinant (r) AAV transgene expression in HeLa cells. Results of the study indicated that hypo-methylation significantly enhanced both wtAAV chromosomal integration and transgene expression of rAAV. A direct influence of methylation on AAV integration was further confirmed by methylating the AAVS1 integration sites prior to viral infection with DNA trans-complementation assay. These results signify the importance of epigenetic status of target cells as one of the key factors in long-term transgene expression in AAV gene therapy.

Indexed as

5-Azacytidineadeno-associated virusgene expressionsite-specific integration

Identifiers

PMID28926997
PMCPMC5615365
OpenAlexW2755707343

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.