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Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector

Overview of attention for article published in Journal of the American Society of Nephrology, July 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#47 of 5,169)
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Citations

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Readers on

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69 Mendeley
Title
Efficient Gene Transfer to Kidney Mesenchymal Cells Using a Synthetic Adeno-Associated Viral Vector
Published in
Journal of the American Society of Nephrology, July 2018
DOI 10.1681/asn.2018040426
Pubmed ID
Authors

Yoichiro Ikeda, Zhao Sun, Xiao Ru, Luk H. Vandenberghe, Benjamin D. Humphreys

Abstract

After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets in vivo; however, protocols for transduction of kidney mesenchymal cells have not been established. We evaluated the transduction profiles of various pseudotyped AAV vectors expressing either GFP or Cre recombinase reporters in mouse kidney and human kidney organoids. Of the six AAVs tested, a synthetic AAV called Anc80 showed specific and high-efficiency transduction of kidney stroma and mesangial cells. We characterized the cell specificity, dose dependence, and expression kinetics and showed the efficacy of this approach by knocking out Gli2 from kidney mesenchymal cells by injection of Anc80-Cre virus into either homozygous or heterozygous Gli2-floxed mice. After unilateral ureteral obstruction, the homozygous Gli2-floxed mice had less fibrosis than the Gli2 heterozygotes had. We observed the same antifibrotic effect in β-catenin-floxed mice injected with Anc80-Cre virus before obstructive injury, strongly supporting a central role for canonical Wnt signaling in kidney myofibroblast activation. Finally, we showed that the Anc80 synthetic virus can transduce the mesenchymal lineage in human kidney organoids. These studies establish a novel method for inducible knockout of floxed genes in mouse mesangium, pericytes, and perivascular fibroblasts and are the foundation for future gene therapy approaches to treat kidney fibrosis.

Twitter Demographics

The data shown below were collected from the profiles of 33 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 69 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 69 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 28%
Researcher 15 22%
Student > Bachelor 6 9%
Other 6 9%
Student > Master 6 9%
Other 6 9%
Unknown 11 16%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 20 29%
Medicine and Dentistry 13 19%
Agricultural and Biological Sciences 13 19%
Engineering 3 4%
Materials Science 2 3%
Other 5 7%
Unknown 13 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 207. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 October 2020.
All research outputs
#133,266
of 21,194,338 outputs
Outputs from Journal of the American Society of Nephrology
#47
of 5,169 outputs
Outputs of similar age
#3,517
of 296,051 outputs
Outputs of similar age from Journal of the American Society of Nephrology
#2
of 70 outputs
Altmetric has tracked 21,194,338 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,169 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.7. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 296,051 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 70 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 98% of its contemporaries.