Evidence map›Paper›PMID 33119640›Full record

ArticlePloS one2020

The effects of PEGylation on LNP based mRNA delivery to the eye.

Renee C Ryals, Siddharth Patel, Chris Acosta, Madison McKinney, Mark E Pennesi, Gaurav Sahay

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

90 citing papers in PubMed, 175 citations in OpenAlex.

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  19. [Research progress on lipid nanoparticle messenger RNA delivery system].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025
    Review
  20. Article

30 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Renee C RyalsDepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
Siddharth PatelDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon, United States of America.
Chris AcostaDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon, United States of America.
Madison McKinneyDepartment of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon, United States of America.
Mark E PennesiDepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.
Gaurav SahayDepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America.ORCID 0000-0003-1071-0500
Oregon State University · USOregon Health & Science University · US

Funding

Proteomics CoreP30EY010572 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Kate E Keller · 1995 to 2026
$19.4M
Overcoming gene delivery barriers to the back of the eyeR21EY031066 · NEI · OREGON STATE UNIVERSITY · PI SAHAY, GAURAV · 2020 to 2021
$421k
NEI NIH HHS P30 EY010572NEI NIH HHS R21 EY031066
6 · The paper itself

Abstract

Gene therapy is now an effective approach to treat many forms of retinal degeneration. Delivery agents that are cell-specific, allow for multiple dosing regimens, and have low immunogenicity are needed to expand the utility of gene therapy for the retina. We generated eight novel lipid nanoparticles (LNPs) ranging in size from 50 nm to 150 nm by changing the PEG content from 5% to 0.5%, respectively. Subretinal injections of LNP-mRNA encoding luciferase revealed that 0.5% PEG content within nanoparticles elicits the highest expression. Similar injections of LNP delivered cre mRNA into Ai9 mice revealed cell-specific protein expression in the retinal pigment epithelium (RPE), confirmed by fundus photography and immunohistochemistry of whole globe cross-sections. To investigate mechanisms of LNP delivery to the eye, we injected mCherry mRNA using the subretinal approach in apoE-/- and Mertk-/- mice. RPE transfection was observed in both mouse models suggesting that LNP intracellular delivery is not solely dependent on apolipoprotein adsorption or phagocytosis. To investigate LNP penetration, particles were delivered to the vitreous chamber via an intravitreal injection. The 0.5% PEG particles mediated the highest luciferase activity and expression was observed in the Müller glia, the optic nerve head and the trabecular meshwork, but failed to reach the RPE. Overall, particles containing less PEG (~150 nm in size) mediated the highest expression in the eye. Thus far, these particles successfully transfect RPE, Müller cells, the optic nerve head and the trabecular meshwork based on route of administration which can expand the utility of LNP-mediated gene therapies for the eye.

Indexed as

Gene Transfer TechniquesAnimalsDrug Delivery SystemsFemaleFundus OculiIntravitreal InjectionsLipidsLuminescent ProteinsMaleMice, Inbred BALB CMice, Inbred C57BLMice, Knockout, ApoENanoparticlesParticle SizePolyethylene GlycolsRed Fluorescent ProteinLipidsLuminescent ProteinsPolyethylene GlycolsRed Fluorescent ProteinRNA, Messenger

Identifiers

PMID33119640
PMCPMC7595320
OpenAlexW3096490487

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Registered trials

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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.