Evidence map›Paper›PMID 34461297›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

AAV integration in human hepatocytes.

Dhwanil A Dalwadi, Andrea Calabria, Amita Tiyaboonchai, Jeffrey Posey, Willscott E Naugler, Eugenio Montini, Markus Grompe

Open access · greenAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
15.6field-weighted citation impact, top 1% 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

81 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Preclinical human models of primary ciliary dyskinesia.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Exploring gene editing as a potential therapeutic strategy for hemophilia.Frontiers in bioengineering and biotechnology · 2026
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Molecular therapy. Nucleic acids · 2025
    Review
  18. Review
  19. AAV-Based Gene Therapy: Opportunities, Risks, and Scale-Up Strategies.International journal of molecular sciences · 2025
    Review
  20. Article

21 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

7 authors at 2 institutions in 2 countries.

Dhwanil A DalwadiPapé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy.
Amita TiyaboonchaiPapé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Jeffrey PoseyPapé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Willscott E NauglerDepartment of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, OR 97239, USA.
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy.
Markus GrompePapé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: grompem@ohsu.edu.
Oregon Health & Science University · USIRCCS Ospedale San Raffaele · IT

Funding

Liver Cancer Risk with rAAV Gene TherapyR01CA190144 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI GROMPE, MARKUS, NAUGLER, WILLSCOTT E · 2015 to 2019
$3.0M
NCI NIH HHS R01 CA190144
6 · The paper itself

Abstract

Recombinant adeno-associated viral (rAAV) vectors are considered promising tools for gene therapy directed at the liver. Whereas rAAV is thought to be an episomal vector, its single-stranded DNA genome is prone to intra- and inter-molecular recombination leading to rearrangements and integration into the host cell genome. Here, we ascertained the integration frequency of rAAV in human hepatocytes transduced either ex vivo or in vivo and subsequently expanded in a mouse model of xenogeneic liver regeneration. Chromosomal rAAV integration events and vector integrity were determined using the capture-PacBio sequencing approach, a long-read next-generation sequencing method that has not previously been used for this purpose. Chromosomal integrations were found at a surprisingly high frequency of 1%-3% both in vitro and in vivo. Importantly, most of the inserted rAAV sequences were heavily rearranged and were accompanied by deletions of the host genomic sequence at the integration site.

Indexed as

Liver RegenerationAnimalsCells, CulturedChromosomesDependovirusDisease Models, AnimalGenetic TherapyGenetic VectorsHepatocytesHumansMiceTransduction, GeneticVirus Integrationcapture sequencingFRGNgenotoxicityrAAVrandom integration

Identifiers

PMID34461297
PMCPMC8531150
OpenAlexW3198142687

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.