Evidence map›Paper›PMID 33732871›Full record

ArticleRegenerative engineering and translational medicine2019

A combinatorial library of biodegradable polyesters enables non-viral gene delivery to post-mitotic human stem cell-derived polarized RPE monolayers.

Bibhudatta Mishra, David R Wilson, Srinivas R Sripathi, Mark P Suprenant, Yuan Rui, Karl J Wahlin, Cynthia A Berlinicke, Jordan J Green, Donald J Zack

Open access · greenAbstract read
In one paragraph

Article in Regenerative engineering and translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

18 citing papers in PubMed, 18 citations in OpenAlex.

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  9. Article
  10. Retinitis pigmentosa and stem cell therapy.International journal of ophthalmology · 2024
    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

9 authors at 1 institution in 1 country.

Bibhudatta MishraOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
David R WilsonBiomedical Engineering, Johns Hopkins University, Baltimore, 21231, United States.
Srinivas R SripathiOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
Mark P SuprenantBiomedical Engineering, Johns Hopkins University, Baltimore, 21231, United States.
Yuan RuiOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
Karl J WahlinOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
Cynthia A BerlinickeOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
Jordan J GreenOphthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, United States.
Donald J ZackInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21231, United States.
Johns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
Screening for Molecules that Promote Photoreceptor SynaptogenesisU01EY027266 · NEI · JOHNS HOPKINS UNIVERSITY · PI GAMM, DAVID M, ZACK, DONALD J. · 2016 to 2018
$2.3M
A High Content Screening Approach for the Retinal Degenerative DiseasesR01EY024249 · NEI · JOHNS HOPKINS UNIVERSITY · PI BERLINICKE, CYNTHIA · 2015 to 2019
$2.0M
Gene Delivery Nanoparticles to Treat GlioblastomaR01CA228133 · NCI · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2019 to 2023
$1.9M
Cancer-specific nanoparticle-mediated gene therapy to treat hepatocellular carcinomaR01EB022148 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2016 to 2019
$1.5M
Sustained Suprachoroidal Delivery of Therapeutic Peptidesfor Ocular DiseasesR21EY026148 · NEI · JOHNS HOPKINS UNIVERSITY · PI CAMPOCHIARO, PETER A, GREEN, JORDAN · 2016 to 2017
$449k
NCI NIH HHS R01 CA228133NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY024249NEI NIH HHS R21 EY026148NEI NIH HHS U01 EY027266NIBIB NIH HHS R01 EB022148
6 · The paper itself

Abstract

Safe and effective delivery of DNA to post-mitotic cells, especially highly differentiated cells, remains a challenge despite significant progress in the development of gene delivery tools. Biodegradable polymeric nanoparticles (NPs) offer an array of advantages for gene delivery over viral vectors due to improved safety, carrying capacity, ease of manufacture, and cell-type specificity. Here we demonstrate the use of a high-throughput screening (HTS) platform to synthesize and screen a library of 148 biodegradable polymeric nanoparticles, successfully identifying structures that enable efficient transfection of human pluripotent stem cell differentiated human retinal pigment epithelial (RPE) cells with minimal toxicity. These NPs can deliver plasmid DNA (pDNA) to RPE monolayers more efficiently than leading commercially available transfection reagents. Novel synthetic polymers are described that enable high efficacy non-viral gene delivery to hard-to-transfect polarized human RPE monolayers, enabling gene loss- and gain-of-function studies of cell signaling, developmental, and disease-related pathways. One new synthetic polymer in particular, 3,3'-iminobis(N,N-dimethylpropylamine)-end terminated poly(1,5-pentanediol diacrylate-co-3 amino-1-propanol) (5-3-J12), was found to form self-assembled nanoparticles when mixed with plasmid DNA that transfect a majority of these human post-mitotic cells with minimal cytotoxicity. The platform described here can be utilized as an enabling technology for gene transfer to human primary and stem cell-derived cells, which are often fragile and resistant to conventional gene transfer approaches.

Indexed as

human stem cellnanoparticlesnon-viral gene therapyophthalmologypoly(beta-amino ester)polymerRetinal pigment epithelial cell

Identifiers

PMID33732871
PMCPMC7962803
OpenAlexW2963585506

What OpenQuestion holds

Textmetadata
LicenceTDM
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.