Evidence map›Paper›PMID 40301362›Full record

ArticleNature communications2025

Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.

K Yu Vlasova, A Kerr, N D Pennock, A Jozic, D K Sahel, M Gautam, N T V Murthy, A Roberts, M W Ali, K D MacDonald and 3 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

K Yu Vlasova *Department of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.
A Kerr *Soft Matter Chemistry, Department of Chemistry and Helsinki Institute of Sustainability Science, Faculty of Science, University of Helsinki, Helsinki, Finland.
N D PennockDepartment of Radiation Medicine, School of Medicine, Oregon Health & Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0001-5374-7843
A JozicDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.ORCID http://orcid.org/0000-0001-6249-2328
D K SahelDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.
M GautamDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.ORCID http://orcid.org/0000-0002-3817-620X
N T V MurthyDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.
A RobertsDepartment of Pediatrics, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
M W AliSoft Matter Chemistry, Department of Chemistry and Helsinki Institute of Sustainability Science, Faculty of Science, University of Helsinki, Helsinki, Finland.
K D MacDonaldDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA.ORCID http://orcid.org/0000-0002-6716-8559
J M WalkerDepartment of Radiation Medicine, School of Medicine, Oregon Health & Science University, Portland, OR, USA.
R LuxenhoferSoft Matter Chemistry, Department of Chemistry and Helsinki Institute of Sustainability Science, Faculty of Science, University of Helsinki, Helsinki, Finland. robert.luxenhofer@helsinki.fi.ORCID http://orcid.org/0000-0001-5567-7404
G SahayDepartment of Pharmaceutical Sciences, College of Pharmacy at Oregon State University, Corvallis, OR, USA. sahay@ohsu.edu.ORCID http://orcid.org/0000-0003-1071-0500

Funding

Nanoparticles based mRNA delivery for treatment of cystic fibrosisR01HL146736 · NHLBI · OREGON STATE UNIVERSITY · PI Gaurav Sahay · 2019 to 2026
$4.5M
Mechanistic insights on structure, topology and radiation effects on RNA nanomedicinesR01CA270783 · NCI · OREGON STATE UNIVERSITY · PI Gaurav Sahay, Conroy Ghin Chee Sun · 2023 to 2026
$2.2M
Cystic Fibrosis Foundation (CF Foundation) SAHAY19XX0NCI NIH HHS R01 CA270783NHLBI NIH HHS R01 HL146736U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01CA270783-01U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL146736
6 · The paper itself

Abstract

We present an efficient method for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to create a library of functional ionizable lipopolymers. Here we show 155 polymers, formulated into polyplexes, to establish structure-activity relationships essential for endosomal escape and transfection. A lead structure is identified, and lipopolymer-lipid hybrid nanoparticles are developed to deliver mRNA to lung endothelium and immune cells, including T cells, with low in vivo toxicity. These nanoparticles show significant improvements in mRNA delivery to the lung compared to in vivo-JetPEI® and demonstrate effective delivery of therapeutic mRNA(s) of various sizes. IL-12 mRNA-loaded nanoparticles delay Lewis Lung cancer progression, while human CFTR mRNA restores CFTR protein function in CFTR knockout mice. Additionally, we demonstrate in vivo CRISPR-Cas9 mRNA delivery, achieving gene editing in lung tissue and successful PD-1 knockout in T cells in mice. These results highlight the platform's potential for systemic gene therapy delivery.

Indexed as

Gene EditingGene Transfer TechniquesLungPolymersAnimalsCRISPR-Cas SystemsCystic Fibrosis Transmembrane Conductance RegulatorGenetic TherapyHumansLipidsMiceMice, Inbred C57BLMice, KnockoutNanoparticlesRNA, MessengerCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorLipidsPolymersRNA, Messenger

Identifiers

PMID40301362
PMCPMC12041268

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.