Evidence map›Paper›PMID 32708811›Full record

ArticlePharmaceutics2020

Avoiding the Pitfalls of siRNA Delivery to the Retinal Pigment Epithelium with Physiologically Relevant Cell Models.

Eva Ramsay, Manuela Raviña, Sanjay Sarkhel, Sarah Hehir, Neil R Cameron, Tanja Ilmarinen, Heli Skottman, Jørgen Kjems, Arto Urtti, Marika Ruponen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
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  5. 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

11 authors at 6 institutions in 6 countries.

Eva RamsayDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Manuela RaviñaDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Sanjay SarkhelDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Sarah HehirDepartment of Life Sciences, Institute of Technology Sligo, F91 YW50 Sligo, Ireland.
Neil R CameronSchool of Engineering, University of Warwick, Coventry CV4 7AL, UK.ORCID 0000-0003-3679-7667
Tanja IlmarinenFaculty of Medicine and Health Technology, BioMediTech, Tampere University, 33014 Tampere, Finland.
Heli SkottmanFaculty of Medicine and Health Technology, BioMediTech, Tampere University, 33014 Tampere, Finland.
Jørgen KjemsInterdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark.
Arto UrttiDrug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Marika RuponenSchool of Pharmacy, University of Eastern Finland, 70210 Kuopio, Finland.
Astrid SubriziInterdisciplinary Nanoscience Center (iNANO), Aarhus University, 8000 Aarhus C, Denmark.ORCID 0000-0003-2170-4333
University of Helsinki · FITampere University · FIUniversity of Eastern Finland · FIAarhus University · DKInstitute of Technology Sligo · IEUniversity of Warwick · GB

Funding

Academy of Finland 323508Leo, Mary and Mary-Ann Hackman Foundation -Lundbeckfonden R181-2014- 3577Seventh Framework Programme 246180
6 · The paper itself

Abstract

Inflammation is involved in the pathogenesis of several age-related ocular diseases, such as macular degeneration (AMD), diabetic retinopathy, and glaucoma. The delivery of anti-inflammatory siRNA to the retinal pigment epithelium (RPE) may become a promising therapeutic option for the treatment of inflammation, if the efficient delivery of siRNA to target cells is accomplished. Unfortunately, so far, the siRNA delivery system selection performed in dividing RPE cells in vitro has been a poor predictor of the in vivo efficacy. Our study evaluates the silencing efficiency of polyplexes, lipoplexes, and lipidoid-siRNA complexes in dividing RPE cells as well as in physiologically relevant RPE cell models. We find that RPE cell differentiation alters their endocytic activity and causes a decrease in the uptake of siRNA complexes. In addition, we determine that melanosomal sequestration is another significant and previously unexplored barrier to gene silencing in pigmented cells. In summary, this study highlights the importance of choosing a physiologically relevant RPE cell model for the selection of siRNA delivery systems. Such cell models are expected to enable the identification of carriers with a high probability of success in vivo, and thus propel the development of siRNA therapeutics for ocular disease.

Indexed as

lipidoidlipoplexmelaninmelanosomephysiologically relevant RPE cell modelpolyplexretinal pigment epitheliumsiRNA delivery

Identifiers

PMID32708811
PMCPMC7407886
OpenAlexW3042238911

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.