Evidence map›Paper›PMID 26169581›Full record

ArticleMolecular imaging and biology2016

Non-Invasive Intravital Imaging of siRNA-Mediated Mutant Keratin Gene Repression in Skin.

Robyn P Hickerson, Tycho J Speaker, Maria Fernanda Lara, Emilio González-González, Manuel A Flores, Christopher H Contag, Roger L Kaspar

Abstract read
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In one paragraph

Article in Molecular imaging and biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 35% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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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

7 authors at 2 institutions in 2 countries.

Robyn P HickersonTransDerm Inc., 2161 Delaware Ave., Santa Cruz, CA, 95060, USA.
Tycho J SpeakerTransDerm Inc., 2161 Delaware Ave., Santa Cruz, CA, 95060, USA.
Maria Fernanda LaraTransDerm Inc., 2161 Delaware Ave., Santa Cruz, CA, 95060, USA.
Emilio González-GonzálezMolecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA.
Manuel A FloresTransDerm Inc., 2161 Delaware Ave., Santa Cruz, CA, 95060, USA.
Christopher H ContagMolecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA, USA.
Roger L KasparTransDerm Inc., 2161 Delaware Ave., Santa Cruz, CA, 95060, USA. roger.kaspar@transderminc.com.
Stanford University · USUniversity of Dundee · GB

Funding

YALE SKIN DISEASES RESEARCH CORE CENTERP30AR041942 · NIAMS · YALE UNIVERSITY · PI TIGELAAR, ROBERT E. · 1992 to 2008
$5.8M
Pachyonychia congenita clinical trial using therapeutic self-delivery siRNAsR44AR056559 · NIAMS · TRANSDERM, INC. · PI KASPAR, ROGER L · 2011 to 2013
$4.1M
Delivery of biologically active nucleic acids to epidermal cellsRC2AR058955 · NIAMS · TRANSDERM, INC. · PI CONTAG, CHRISTOPHER H, KASPAR, ROGER L · 2009 to 2010
$2.8M
NIAMS NIH HHS P30 AR041942NIAMS NIH HHS R44AR056559NIAMS NIH HHS RC2 AR058955
6 · The paper itself

Abstract

purposeSmall interfering RNAs (siRNAs) specifically and potently inhibit target gene expression. Pachyonychia congenita (PC) is a skin disorder caused by mutations in genes encoding keratin (K) 6a/b, K16, and K17, resulting in faulty intermediate filaments. A siRNA targeting a single nucleotide, PC-relevant mutation inhibits K6a expression and has been evaluated in the clinic with encouraging results. PROCEDURES: To better understand the pathophysiology of PC, and develop a model system to study siRNA delivery and visualize efficacy in skin, wild type (WT) and mutant K6a complementary DNAs (cDNAs) were fused to either enhanced green fluorescent protein or tandem tomato fluorescent protein cDNA to allow covisualization of mutant and WT K6a expression in mouse footpad skin using a dual fluorescence in vivo confocal imaging system equipped with 488 and 532 nm lasers.

resultsExpression of mutant K6a/reporter resulted in visualization of keratin aggregates, while expression of WT K6a/reporter led to incorporation into filaments. Addition of mutant K6a-specific siRNA resulted in inhibition of mutant, but not WT, K6a/reporter expression.

conclusionsIntravital imaging offers subcellular resolution for tracking functional activity of siRNA in real time and enables detailed analyses of therapeutic effects in individual mice to facilitate development of nucleic acid-based therapeutics for skin disorders.

Indexed as

Gene ExpressionAnimalsCell LineGenes, ReporterGreen Fluorescent ProteinsHumansInjections, IntradermalKeratinsMiceMolecular ImagingMutant ProteinsMutationPlasmidsProtein AggregatesRepressor ProteinsRNA, Small Interferingenhanced green fluorescent proteinGreen Fluorescent ProteinsKeratinsMutant ProteinsProtein AggregatesRepressor ProteinsRNA, Small InterferingGene regulationGene therapyGenodermatosisIn vivo confocal fluorescence microscopy

Identifiers

PMID26169581
OpenAlexW2175870611

What OpenQuestion holds

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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.