Evidence map›Paper›PMID 31803860›Full record

ArticleAPL bioengineering2019

AAV-mediated gene therapy targeting TRPV4 mechanotransduction for inhibition of pulmonary vascular leakage.

Juan Li, Amy M Wen, Ratnakar Potla, Ezekiel Benshirim, Ariel Seebarran, Maximilian A Benz, Olivier Y F Henry, Benjamin D Matthews, Rachelle Prantil-Baun, Sarah E Gilpin and 2 more

Open access · goldAbstract read
In one paragraph

Article in APL bioengineering, 2019. 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
2.6field-weighted citation impact, top 12% 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, 29 citations in OpenAlex.

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  4. An alveolus lung-on-a-chip model ofbioRxiv : the preprint server for biology · 2025
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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

12 authors at 2 institutions in 2 countries.

Juan LiWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Amy M WenWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.ORCID https://orcid.org/0000-0002-6740-9906
Ratnakar Potla
Ezekiel Benshirim
Ariel Seebarran
Maximilian A BenzWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.ORCID https://orcid.org/0000-0002-8295-4996
Olivier Y F HenryWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Benjamin D Matthews
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Sarah E GilpinWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Oren LevyWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts 02115, USA.
Harvard University · USBoston Children's Hospital · US

Funding

Mechanotransduction analysis in a microengineered lung-on-a-chipR01EB020004 · NIBIB · HARVARD MEDICAL SCHOOL · PI INGBER, DONALD E · 2015 to 2018
$2.5M
Lung-on-a-chip pulmonary fibrosis model for drug discoveryF32HL146070 · NHLBI · HARVARD UNIVERSITY · PI WEN, AMY · 2019 to 2019
$35k
NHLBI NIH HHS F32 HL146070NIBIB NIH HHS R01 EB020004
6 · The paper itself

Abstract

Enhanced vascular permeability in the lungs can lead to pulmonary edema, impaired gas exchange, and ultimately respiratory failure. While oxygen delivery, mechanical ventilation, and pressure-reducing medications help alleviate these symptoms, they do not treat the underlying disease. Mechanical activation of transient receptor potential vanilloid 4 (TRPV4) ion channels contributes to the development of pulmonary vascular disease, and overexpression of the high homology (HH) domain of the TRPV4-associated transmembrane protein CD98 has been shown to inhibit this pathway. Here, we describe the development of an adeno-associated virus (AAV) vector encoding the CD98 HH domain in which the AAV serotypes and promoters have been optimized for efficient and specific delivery to pulmonary cells. AAV-mediated gene delivery of the CD98 HH domain inhibited TRPV4 mechanotransduction in a specific manner and protected against pulmonary vascular leakage in a human lung Alveolus-on-a-Chip model. As AAV has been used clinically to deliver other gene therapies, these data raise the possibility of using this type of targeted approach to develop mechanotherapeutics that target the TRPV4 pathway for treatment of pulmonary edema in the future.

Identifiers

PMID31803860
PMCPMC6887658
OpenAlexW2991747883

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.