Evidence map›Paper›PMID 25965395›Full record

ArticleGene therapy2015

Local administration of AAV-DJ pseudoserotype expressing COX2 provided early onset of transgene expression and promoted bone fracture healing in mice.

R Lakhan, D J Baylink, K-H W Lau, X Tang, M H-C Sheng, C H Rundle, X Qin

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  6. Curative Cell and Gene Therapy for Osteogenesis Imperfecta.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Review
  7. Review
  8. STAR protocols · 2021
    Article
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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 1 country.

R LakhanDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
D J BaylinkDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
K-H W LauDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
X TangDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
M H-C ShengDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
C H RundleMusculoskeletal Disease Center, Jerry L Pettis Memorial VA Medical Center, Loma Linda, CA, USA.
X QinDivision of Regenerative Medicine, Department of Medicine, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Loma Linda University · USJerry L. Pettis Memorial VA Medical Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We have previously obtained compelling proof-of-principle evidence for COX2 gene therapy for fracture repair using integrating retroviral vectors. For this therapy to be suitable for patient uses, a suitable vector with high safety profile must be used. Accordingly, this study sought to evaluate the feasibility of AAV as the vector for this COX2 gene therapy, because AAV raises less safety issues than the retroviral vectors used previously. However, an appropriate AAV serotype is required to provide early increase in and adequate level of COX2 expression that is needed for fracture repair. Herein, we reported that AAV-DJ, an artificial AAV pseudoserotype, is highly effective in delivering COX2 gene to fracture sites in a mouse femoral fracture model. Compared with AAV-2, the use of AAV-DJ led to ~5-fold increase in infectivity in mesenchymal stem cells (MSCs) and provided an earlier and significantly higher level of transgene expression at the fracture site. Injection of this vector at a dose of 7.5 × 10(11) genomic copies led to high COX2 level at the fracture site on day 3 after injections and significantly promoted fracture union at 21 days, as analyzed by radiography and μ-CT. The therapeutic effect appears to involve enhanced osteoblastic differentiation of MSCs and remodeling of callus tissues to laminar bone. This interpretation is supported by the enhanced expression of several key genes participating in the fracture repair process. In conclusion, AAV-DJ is a promising serotype for the AAV-based COX2 gene therapy of fracture repair in humans.

Indexed as

Fracture HealingTransgenesAnimalsCyclooxygenase 2DependovirusDisease Models, AnimalGenetic TherapyGenetic VectorsMaleMice, Inbred C57BLTibiaCyclooxygenase 2Ptgs2 protein, mouse

Identifiers

PMID25965395
OpenAlexW1607008970

What OpenQuestion holds

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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.