Evidence map›Paper›PMID 33320893›Full record

ArticlePloS one2020

Comparative intra-articular gene transfer of seven adeno-associated virus serotypes reveals that AAV2 mediates the most efficient transduction to mouse arthritic chondrocytes.

Quan Chen, Huan Luo, Chengcong Zhou, Huan Yu, Sai Yao, Fangda Fu, Rebecca Seeley, Xing Ji, Yanping Yang, Peifeng Chen and 6 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  8. Rationally engineered novel AAV capsids for intra-articular gene delivery.Molecular therapy. Methods & clinical development · 2024
    Article
  9. Article
  10. Article
  11. Viral Gene Delivery in Chondrocytes.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  12. AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  13. 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

16 authors at 5 institutions in 2 countries.

Quan ChenThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Huan LuoDepartment of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Chengcong ZhouThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Huan YuThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Sai YaoThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Fangda FuThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Rebecca SeeleyTranslational Research Program in Pediatric Orthopedics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.ORCID 0000-0002-1711-8828
Xing JiTranslational Research Program in Pediatric Orthopedics, The Children's Hospital of Philadelphia, Philadelphia, PA, United States of America.
Yanping YangLonghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Peifeng ChenThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Hongting JinThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Peijian TongThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Di ChenResearch Center for Human Tissues and Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chengliang WuThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Weibin DuResearch Institute of Orthopedics, the Affiliated JiangNan Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Hongfeng RuanThe First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.ORCID 0000-0001-8868-9313
Zhejiang Chinese Medical University · CNChildren's Hospital of Philadelphia · USChinese Academy of Sciences · CNSecond Affiliated Hospital of Zhejiang University · CNShanghai University of Traditional Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoarthritis (OA) is the most common arthropathy, characterized by progressive degeneration of the articular cartilage. Currently, there are no disease-modifying approaches for OA treatment. Adeno-associated virus (AAV)-mediated gene therapy has recently become a potential treatment for OA due to its exceptional characteristics; however, the tropism and transduction efficiency of different AAV serotypes to articular joints and the safety profile of AAV applications are still unknown. The present study aims to screen an ideal AAV serotype to efficiently transfer genes to arthritic cartilage. AAV vectors of different serotypes expressing eGFP protein were injected into the knee joint cavities of mice, with all joint tissues collected 30 days after AAV injection. The transduction efficiency of AAVs was quantified by assessing the fluorescent intensities of eGFP in the cartilage of knee joints. Structural and morphological changes were analyzed by toluidine blue staining. Changes to ECM metabolism and pyroptosis of chondrocytes were determined by immunohistochemical staining. Fluorescence analysis of eGFP showed that eGFP was expressed in the cartilage of knee joints injected with each AAV vector. Quantification of eGFP intensity indicated that AAV2, 7 and 8 had the highest transduction efficiencies. Both toluidine blue staining and Mankin score showed that AAV6 aggravated cartilage degeneration. The analysis of key molecules in ECM metabolism suggested that AAV5 and 7 significantly reduced collagen type II, while AAV9 increased ADAMTS-4 but decreased MMP-19. In addition, transduction with AAV2, 5, 7 and 8 had no obvious effect on pyroptosis of chondrocytes. Comprehensive score analysis also showed that AAV2 had the highest score in intra-articular gene transfer. Collectively, our findings point to AAV2 as the best AAV serotype candidate for gene transfer on arthritic cartilage, resulting in minimal impact to ECM metabolism and pyroptosis of chondrocytes.

Indexed as

Arthritis, ExperimentalGenetic TherapyGenetic VectorsParvovirinaeADAMTS4 ProteinAnimalsCartilage, ArticularChondrocytesCollagen Type IIDependovirusKnee JointMaleMatrix Metalloproteinases, SecretedMiceTransduction, GeneticADAMTS4 ProteinAdamts4 protein, mouseCollagen Type IImatrix metalloproteinase 19Matrix Metalloproteinases, Secreted

Identifiers

PMID33320893
PMCPMC7737971
OpenAlexW3111209037

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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.