Evidence map›Paper›PMID 32123081›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Sonoselective transfection of cerebral vasculature without blood-brain barrier disruption.

Catherine M Gorick, Alexander S Mathew, William J Garrison, E Andrew Thim, Delaney G Fisher, Caitleen A Copeland, Ji Song, Alexander L Klibanov, G Wilson Miller, Richard J Price

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Sonoselective Transfection of Glioma Endothelium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  12. The blood-brain barrier: structure, regulation, and drug delivery.Signal transduction and targeted therapy · 2023
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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

10 authors at 1 institution in 1 country.

Catherine M GorickDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Alexander S MathewDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
William J GarrisonDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
E Andrew ThimDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Delaney G FisherDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Caitleen A CopelandDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Ji SongDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Alexander L KlibanovDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
G Wilson MillerDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908.
Richard J PriceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908; rprice@virginia.edu.ORCID 0000-0002-0237-2102
University of Virginia · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
MRI-Guided miRNA Nanoparticle Delivery to Glioblastoma With Focused UltrasoundR01EB020147 · NIBIB · UNIVERSITY OF VIRGINIA · PI HANES, JUSTIN S., PRICE, RICHARD J. · 2015 to 2018
$2.4M
Endothelial DNA Methylation, Arteriogenic Capacity, and Shear Stress "Set-Point."R21EB024323 · NIBIB · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2017 to 2018
$442k
Leveraging Focused Ultrasound to Sensitize Refractory Melanoma to ImmunotherapyF30CA247254 · NCI · UNIVERSITY OF VIRGINIA · PI MATHEW, ALEXANDER SEAN · 2020 to 2022
$138k
NIBIB NIH HHS R01 EB020147NIBIB NIH HHS R21 EB024323NIGMS NIH HHS T32 GM007267
6 · The paper itself

Abstract

Treatment of many pathologies of the brain could be improved markedly by the development of noninvasive therapeutic approaches that elicit robust, endothelial cell-selective gene expression in specific brain regions that are targeted under MR image guidance. While focused ultrasound (FUS) in conjunction with gas-filled microbubbles (MBs) has emerged as a noninvasive modality for MR image-guided gene delivery to the brain, it has been used exclusively to transiently disrupt the blood-brain barrier (BBB), which may induce a sterile inflammation response. Here, we introduce an MR image-guided FUS method that elicits endothelial-selective transfection of the cerebral vasculature (i.e., "sonoselective" transfection), without opening the BBB. We first determined that activating circulating, cationic plasmid-bearing MBs with pulsed low-pressure (0.1 MPa) 1.1-MHz FUS facilitates sonoselective gene delivery to the endothelium without MRI-detectable disruption of the BBB. The degree of endothelial selectivity varied inversely with the FUS pressure, with higher pressures (i.e., 0.3-MPa and 0.4-MPa FUS) consistently inducing BBB opening and extravascular transfection. Bulk RNA sequencing analyses revealed that the sonoselective low-pressure regimen does not up-regulate inflammatory or immune responses. Single-cell RNA sequencing indicated that the transcriptome of sonoselectively transfected brain endothelium was unaffected by the treatment. The approach developed here permits targeted gene delivery to blood vessels and could be used to promote angiogenesis, release endothelial cell-secreted factors to stimulate nerve regrowth, or recruit neural stem cells.

Indexed as

Ultrasonic WavesAnimalsBlood-Brain BarrierMagnetic Resonance ImagingMaleMiceMice, Inbred C57BLMicrobubblesTranscriptomeTransfectionendotheliumfocused ultrasoundgene deliverymicrobubbles

Identifiers

PMID32123081
PMCPMC7084076
OpenAlexW3009105183

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.