Evidence map›Paper›PMID 34834329›Full record

ArticlePharmaceutics2021

Hydrophobic Optimization of Functional Poly(TPAE-co-suberoyl chloride) for Extrahepatic mRNA Delivery following Intravenous Administration.

Xueliang Yu, Shuai Liu, Qiang Cheng, Sang M Lee, Tuo Wei, Di Zhang, Lukas Farbiak, Lindsay T Johnson, Xu Wang, Daniel John Siegwart

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

10 authors at 1 institution in 1 country.

Xueliang YuDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Shuai LiuDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Qiang ChengDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sang M LeeDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Tuo WeiDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0002-2823-9721
Di ZhangDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lukas FarbiakDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Lindsay T JohnsonDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xu WangDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Daniel John SiegwartDepartment of Biochemistry, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
The University of Texas Southwestern Medical Center · US

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7M
Defining the molecular interactions within nanoparticles that enable delivery of long nucleic acidsR01EB025192 · NIBIB · UT SOUTHWESTERN MEDICAL CENTER · PI SIEGWART, DANIEL JOHN · 2018 to 2025
$3.1M
Chemistry-Biology Interface T32T32GM127216 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI KOHLER, JENNIFER J, PHILLIPS, MARGARET A. · 2019 to 2023
$754k
Magnetorotation: a Rapid Assay for Single Cell Drug Sensitivity of Cancer CellsR21CA160157 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOPELMAN, RAOUL · 2011 to 2012
$276k
NIBIB NIH HHS R01 EB025192NIGMS NIH HHS T32 GM127216NIH HHS P30 CA142543NIH HHS R01 EB025192-01A1NIH HHS T32GM127216
6 · The paper itself

Abstract

Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared to other nucleic acids (e.g., siRNA and pDNA), there are more opportunities to improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library of 1200 functional polyesters for systemic mRNA delivery. We focused on the chemical investigation of hydrophobic optimization as a method to adjust mRNA polyplex stability, diameter, pKa, and efficacy. Focusing on a region of the library heatmap (PE4K-A17), we further explored the delivery of luciferase mRNA to IGROV1 ovarian cancer cells in vitro and to C57BL/6 mice in vivo following intravenous administration. PE4K-A17-0.2C8 was identified as an efficacious carrier for delivering mRNA to mouse lungs. The delivery selectivity between organs (lungs versus spleen) was found to be tunable through chemical modification of polyesters (both alkyl chain length and molar ratio in the formulation). Cre recombinase mRNA was delivered to the Lox-stop-lox tdTomato mouse model to study potential application in gene editing. Overall, we identified a series of polymer-mRNA polyplexes stabilized with Pluronic F-127 for safe and effective delivery to mouse lungs and spleens. Structure-activity relationships between alkyl side chains and in vivo delivery were elucidated, which may be informative for the continued development of polymer-based mRNA delivery.

Indexed as

Cre recombinase mRNAluciferase mRNAmRNA deliverynanoparticlespolyesterspolyplex

Identifiers

PMID34834329
PMCPMC8624493
OpenAlexW3212316750

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.