Evidence map›Paper›PMID 22480249›Full record

ArticleHuman gene therapy2012

Inhibition of CD44 gene expression in human skin models, using self-delivery short interfering RNA administered by dissolvable microneedle arrays.

Maria Fernanda Lara, Emilio González-González, Tycho J Speaker, Robyn P Hickerson, Devin Leake, Leonard M Milstone, Christopher H Contag, Roger L Kaspar

Open access · greenAbstract read
In one paragraph

Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Transdermal delivery for gene therapy.Drug delivery and translational research · 2022
    Review
  5. Article
  6. Smart Microneedles for Therapy and Diagnosis.Research (Washington, D.C.) · 2020
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. In vivo gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation.Journal of controlled release : official journal of the Controlled Release Society · 2014
    Article
  16. Article
  17. Review
  18. Gene silencing following siRNA delivery to skin via coated steel microneedles: In vitro and in vivo proof-of-concept.Journal of controlled release : official journal of the Controlled Release Society · 2013
    Article
  19. Review
  20. Article
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

8 authors at 4 institutions in 2 countries.

Maria Fernanda LaraTransDerm, Santa Cruz, CA 95060, USA.
Emilio González-González
Tycho J Speaker
Robyn P Hickerson
Devin Leake
Leonard M Milstone
Christopher H Contag
Roger L Kaspar
University of California, Santa Cruz · USStanford University · USThermo Fisher Scientific (United States) · USYale University · US

Funding

Delivery of biologically active nucleic acids to epidermal cellsRC2AR058955 · NIAMS · TRANSDERM, INC. · PI CONTAG, CHRISTOPHER H, KASPAR, ROGER L · 2009 to 2010
$2.8M
Evaluation of siRNA uptake and functional activity in a human organotypic skin moR43AR059474 · NIAMS · TRANSDERM, INC. · PI KASPAR, ROGER L · 2010 to 2010
$341k
NIAMS NIH HHS R43AR059474NIAMS NIH HHS RC2AR058955-02
6 · The paper itself

Abstract

Treatment of skin disorders with short interfering RNA (siRNA)-based therapeutics requires the development of effective delivery methodologies that reach target cells in affected tissues. Successful delivery of functional siRNA to the epidermis requires (1) crossing the stratum corneum, (2) transfer across the keratinocyte membrane, followed by (3) incorporation into the RNA-induced silencing complex. We have previously demonstrated that treatment with microneedle arrays loaded with self-delivery siRNA (sd-siRNA) can achieve inhibition of reporter gene expression in a transgenic mouse model. Furthermore, treatment of human cultured epidermal equivalents with sd-siRNA resulted in inhibition of target gene expression. Here, we demonstrate inhibition of CD44, a gene that is uniformly expressed throughout the epidermis, by sd-siRNA both in vitro (cultured human epidermal skin equivalents) and in vivo (full-thickness human skin equivalents xenografted on immunocompromised mice). Treatment of human skin equivalents with CD44 sd-siRNA markedly decreased CD44 mRNA levels, which led to a reduction of the target protein as confirmed by immunodetection in epidermal equivalent sections with a CD44-specific antibody. Taken together, these results demonstrate that sd-siRNA, delivered by microneedle arrays, can reduce expression of a targeted endogenous gene in a human skin xenograft model.

Indexed as

AnimalsCells, CulturedFemaleGene ExpressionGenes, ReporterHumansHyaluronan ReceptorsImmunohistochemistryKeratinocytesMiceMice, SCIDNeedlesPolymethyl MethacrylatePolyvinyl AlcoholRNA, Small InterferingSkinCD44 protein, humanHyaluronan ReceptorsPolymethyl MethacrylatePolyvinyl AlcoholRNA, Small Interfering

Identifiers

PMID22480249
PMCPMC3413896
OpenAlexW2039810674

What OpenQuestion holds

Textmetadata
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.