Evidence map›Paper›PMID 28088460›Full record

ArticleGastroenterology2017

Ultrasound-Mediated Delivery of RNA to Colonic Mucosa of Live Mice.

Carl M Schoellhammer, Gregory Y Lauwers, Jeremy A Goettel, Matthias A Oberli, Cody Cleveland, June Y Park, Daniel Minahan, Yiyun Chen, Daniel G Anderson, Ana Jaklenec and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 58 citations in OpenAlex.

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  13. Foundations of gastrointestinal-based drug delivery and future developments.Nature reviews. Gastroenterology & hepatology · 2022
    Review
  14. Article
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  17. Article
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  19. siRNA Targeting and Treatment of Gastrointestinal Diseases.Clinical and translational science · 2019
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Carl M SchoellhammerDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Gregory Y LauwersGastrointestinal Pathology Service, H. Lee Moffitt Cancer Center and Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida.
Jeremy A GoettelDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts.
Matthias A OberliDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Cody ClevelandThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
June Y ParkDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Daniel MinahanThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Yiyun ChenThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; Department of Materials, University of Oxford, Oxford, United Kingdom.
Daniel G AndersonDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts; Harvard-Massachusetts Institute of Technology Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Ana JaklenecThe David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
Scott B SnapperDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts; Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Robert LangerDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts; Harvard-Massachusetts Institute of Technology Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts. Electronic address: rlanger@mit.edu.
Giovanni TraversoDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts; Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: ctraverso@partners.org.
Massachusetts Institute of Technology · USBrigham and Women's Hospital · USBoston Children's Hospital · USUniversity of Oxford · GBUniversity of South Florida · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
CONTROLLED RELEASE OF MACROMOLECULESR01EB000244 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LANGER, ROBERT SAMUEL, TRAVERSO, CARLO GIOVANNI · 2002 to 2021
$6.1M
Controlled Release of MacromoleculesR37EB000244 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LANGER, ROBERT SAMUEL · 2008 to 2017
$3.9M
NIBIB NIH HHS R01 EB000244NIBIB NIH HHS R37 EB000244NIDDK NIH HHS P30 DK034854
6 · The paper itself

Abstract

BACKGROUND &

aimsIt is a challenge to deliver nucleic acids to gastrointestinal (GI) tissues due to their size and need for intracellular delivery. They are also extremely susceptible to degradation by nucleases, which are ubiquitous in the GI tract. We investigated whether ultrasound, which can permeabilize tissue through a phenomenon known as transient cavitation, can be used to deliver RNA to the colonic mucosa of living mice.

methodsWe investigated delivery of fluorescently labeled permeants to colon tissues of Yorkshire pigs ex vivo and mice in vivo. Colon tissues were collected and fluorescence was measured by confocal microscopy. We then evaluated whether ultrasound is effective in delivering small interfering (si)RNA to C57BL/6 mice with dextran sodium sulfate-induced colitis. Some mice were given siRNA against tumor necrosis factor (Tnf) mRNA for 6 days; colon tissues were collected and analyzed histologically and TNF protein levels measured by enzyme-linked immunosorbent assay. Feces were collected and assessed for consistency and occult bleeding. We delivered mRNA encoding firefly luciferase to colons of healthy C57BL/6 mice.

resultsExposure of ex vivo pig colon tissues to 20 kHz ultrasound for 1 minute increased the level of delivery of 3 kDa dextran 7-fold compared with passive diffusion (P = .037); 40 kHz ultrasound application for 0.5 seconds increased the delivery 3.3-fold in living mice (P = .041). Confocal microscopy analyses of colon tissues from pigs revealed regions of punctuated fluorescent dextran signal, indicating intracellular delivery of macromolecules. In mice with colitis, ultrasound delivery of unencapsulated siRNA against Tnf mRNA reduced protein levels of TNF in colon tissues, compared with mice with colitis given siRNA against Tnf mRNA without ultrasound (P ≤ .014), and reduced features of inflammation (P ≤ 4.1 × 10

conclusionsUltrasound can be used to deliver mRNAs and siRNAs to the colonic mucosa of mice and knock down expression of target mRNAs.

Indexed as

PermeabilityAnimalsColitisColonDextran SulfateDrug Delivery SystemsIntestinal MucosaLuciferases, FireflyMiceMice, Inbred C57BLMicroscopy, ConfocalRNA, MessengerRNA, Small InterferingSus scrofaSwineTumor Necrosis Factor-alphaDextran SulfateLuciferases, FireflyRNA, MessengerRNA, Small InterferingTumor Necrosis Factor-alphaAntisense TherapyInflammatory Bowel DiseaseUlcerative ColitisUltrasound-Mediated Gastrointestinal Drug Delivery

Identifiers

PMID28088460
PMCPMC5368009
OpenAlexW2572531120

What OpenQuestion holds

Textmetadata
LicenceTDM
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.