Evidence map›Paper›PMID 34435198›Full record

ArticleBiology open2021

Specificity and off-target effects of AAV8-TBG viral vectors for the manipulation of hepatocellular gene expression in mice.

Christos Kiourtis, Ania Wilczynska, Colin Nixon, William Clark, Stephanie May, Thomas G Bird

Open access · goldAbstract read
In one paragraph

Article in Biology open, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
7.3field-weighted citation impact, top 2% 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

42 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Human FGF1Cells · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Genetic synchronization of the brain and liver molecular clocks defend against chrono-metabolic disease.Proceedings of the National Academy of Sciences of the United States of America · 2024
    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

6 authors at 1 institution in 1 country.

Christos KiourtisCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.ORCID 0000-0002-6682-5668
Ania WilczynskaCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.ORCID 0000-0003-4548-9367
Colin NixonCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
William ClarkCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
Stephanie MayCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.ORCID 0000-0003-0095-7403
Thomas G BirdCancer Research UK Beatson Institute, Glasgow G61 1BD, UK.ORCID 0000-0002-6120-1581
Cancer Research UK Scotland Institute · GB

Funding

Cancer Research UK 26813Cancer Research UK A17196The Wellcome Trust WT107492ZWellcome Trust
6 · The paper itself

Abstract

Mice are a widely used pre-clinical model system in large part due to their potential for genetic manipulation. The ability to manipulate gene expression in specific cells under temporal control is a powerful experimental tool. The liver is central to metabolic homeostasis and a site of many diseases, making the targeting of hepatocytes attractive. Adeno-associated virus 8 (AAV8) vectors are valuable instruments for the manipulation of hepatocellular gene expression. However, their off-target effects in mice have not been thoroughly explored. Here, we sought to identify the short-term off-target effects of AAV8 administration in mice. To do this, we injected C57BL/6J wild-type mice with either recombinant AAV8 vectors expressing Cre recombinase or control AAV8 vectors and characterised the changes in general health and in liver physiology, histology and transcriptomics compared to uninjected controls. We observed an acute and transient trend for reduction in homeostatic liver proliferation together with induction of the DNA damage marker γH2AX following AAV8 administration. The latter was enhanced upon Cre recombinase expression by the vector. Furthermore, we observed transcriptional changes in genes involved in circadian rhythm and response to infection. Notably, there were no additional transcriptomic changes upon expression of Cre recombinase by the AAV8 vector. Overall, there was no evidence of liver injury, and only mild T-cell infiltration was observed 14 days following AAV8 infection. These data advance the technique of hepatocellular genome editing through Cre-Lox recombination using Cre expressing AAV vectors, demonstrating their minimal effects on murine physiology and highlight the more subtle off target effects of these systems.

Indexed as

DependovirusAnimalsCarcinoma, HepatocellularCell ProliferationDisease Models, AnimalGene ExpressionGenetic VectorsIntegrasesLiverLiver NeoplasmsMiceMice, Inbred C57BLCre recombinaseIntegrasesAdeno-associated virusGenetic modelsLiver diseaseMouse model

Identifiers

PMID34435198
PMCPMC8487635
OpenAlexW3195101435

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.