Evidence map›Paper›PMID 30301666›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018

Development of Targeted siRNA Nanocomplexes to Prevent Fibrosis in Experimental Glaucoma Filtration Surgery.

Owen Fernando, Aristides D Tagalakis, Sahar Awwad, Steve Brocchini, Peng T Khaw, Stephen L Hart, Cynthia Yu-Wai-Man

Open access · hybridAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. 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
2.2field-weighted citation impact, top 11% 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, 50 citations in OpenAlex.

  1. Article
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  6. Molecular and functional correction of a deep intronic splicing mutation inMolecular therapy. Methods & clinical development · 2023
    Article
  7. Efficient ocular delivery of siRNAInternational journal of pharmaceutics: X · 2023
    Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
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  15. Article
  16. O-GlcNAcylation inhibits hepatic stellate cell activation.Journal of gastroenterology and hepatology · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. Review
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 5 institutions in 1 country.

Owen FernandoNational Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK.
Aristides D TagalakisExperimental and Personalised Medicine Section, Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Department of Biology, Edge Hill University, Ormskirk L39 4QP, UK.
Sahar AwwadNational Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK; UCL School of Pharmacy, London WC1N 1AX, UK.
Steve BrocchiniNational Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK; UCL School of Pharmacy, London WC1N 1AX, UK.
Peng T KhawNational Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK.
Stephen L HartExperimental and Personalised Medicine Section, Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Cynthia Yu-Wai-ManNational Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London EC1V 2PD, UK; King's College London, London SE1 7EH, UK. Electronic address: c.yu-wai-man@ucl.ac.uk.
Great Ormond Street Hospital · GBMoorfields Eye Hospital NHS Foundation Trust · GBNational Institute for Health Research · GBThe London College · GBUniversity College London · GB

Funding

Medical Research Council MC_PC_15037
6 · The paper itself

Abstract

RNAi induced by double-stranded small interfering RNA (siRNA) molecules has attracted great attention as a naturally occurring approach to silence gene expression with high specificity. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is a master regulator of cytoskeletal gene expression and, thus, represents a promising target to prevent fibrosis. A major hurdle to implementing siRNA therapies is the method of delivery, and we have, thus, optimized lipid-peptide-siRNA (LPR) nanoparticles containing MRTF-B siRNAs as a targeted approach to prevent conjunctival fibrosis. We tested 15 LPR nanoparticle formulations with different lipid compositions, surface charges, and targeting or non-targeting peptides in human conjunctival fibroblasts. In vitro, the LPR formulation of the DOTMA/DOPE lipid with the targeting peptide Y (LYR) was the most efficient in MRTF-B gene silencing and non-cytotoxic compared to the non-targeting formulation. In vivo, subconjunctival administration of LYR nanoparticles containing MRTF-B siRNAs doubled bleb survival in a pre-clinical rabbit model of glaucoma filtration surgery. Furthermore, MRTF-B LYR nanoparticles reduced the MRTF-B mRNA by 29.6% in rabbit conjunctival tissues, which led to significantly decreased conjunctival scarring with no adverse side effects. LYR-mediated delivery of siRNA shows promising results to increase bleb survival and to prevent conjunctival fibrosis after glaucoma filtration surgery.

Indexed as

NanostructuresAnimalsBiophysical PhenomenaBiopsyDisease Models, AnimalFibroblastsFibrosisFiltering SurgeryGene SilencingGlaucomaHumansLiposomesNanoparticlesPeptidesRabbitsRNA, Small InterferingLiposomesPeptidesRNA, Small InterferingfibrosisglaucomananoparticlesiRNAtargeting peptide

Identifiers

PMID30301666
PMCPMC6277485
OpenAlexW2891665442

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.