Evidence map›Paper›PMID 36038136›Full record

ArticleACS nano2022

Engineering Lipid Nanoparticles for Enhanced Intracellular Delivery of mRNA through Inhalation.

Jeonghwan Kim, Antony Jozic, Yuxin Lin, Yulia Eygeris, Elissa Bloom, Xiaochen Tan, Christopher Acosta, Kelvin D MacDonald, Kevin D Welsher, Gaurav Sahay

Open access · greenAbstract read
In one paragraph

Article in ACS nano, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed
18.1field-weighted citation impact, top 1% 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

128 citing papers in PubMed, 235 citations in OpenAlex.

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  12. Considerations for early life genetic therapies in cystic fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2026
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68 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

10 authors at 3 institutions in 1 country.

Jeonghwan KimDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.ORCID 0000-0002-1697-5107
Antony JozicDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.ORCID 0000-0001-6249-2328
Yuxin LinDepartment of Chemistry, Duke University, Durham, North Carolina 27708, United States.
Yulia EygerisDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.
Elissa BloomDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.
Xiaochen TanDepartment of Chemistry, Duke University, Durham, North Carolina 27708, United States.ORCID 0000-0001-7694-5391
Christopher AcostaDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.
Kelvin D MacDonaldDepartment of Pediatrics, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, United States.
Kevin D WelsherDepartment of Chemistry, Duke University, Durham, North Carolina 27708, United States.ORCID 0000-0002-3180-279X
Gaurav SahayDepartment of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, United States.ORCID 0000-0003-1071-0500
Oregon State University · USDuke University · USOregon Health & Science University · US

Funding

Nanoparticles based mRNA delivery for treatment of cystic fibrosisR01HL146736 · NHLBI · OREGON STATE UNIVERSITY · PI Gaurav Sahay · 2019 to 2026
$4.5M
NHLBI NIH HHS R01 HL146736
6 · The paper itself

Abstract

Despite lipid nanoparticles' (LNPs) success in the effective and safe delivery of mRNA vaccines, an inhalation-based mRNA therapy for lung diseases remains challenging. LNPs tend to disintegrate due to shear stress during aerosolization, leading to ineffective delivery. Therefore, LNPs need to remain stable through the process of nebulization and mucus penetration, yet labile enough for endosomal escape. To meet these opposing needs, we utilized PEG lipid to enhance the surficial stability of LNPs with the inclusion of a cholesterol analog, β-sitosterol, to improve endosomal escape. Increased PEG concentrations in LNPs enhanced the shear resistance and mucus penetration, while β-sitosterol provided LNPs with a polyhedral shape, facilitating endosomal escape. The optimized LNPs exhibited a uniform particle distribution, a polyhedral morphology, and a rapid mucosal diffusion with enhanced gene transfection. Inhaled LNPs led to localized protein production in the mouse lung without pulmonary or systemic toxicity. Repeated administration of these LNPs led to sustained protein production in the lungs. Lastly, mRNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) was delivered after nebulization to a CFTR-deficient animal model, resulting in the pulmonary expression of this therapeutic protein. This study demonstrated the rational design approach for clinical translation of inhalable LNP-based mRNA therapies.

Indexed as

Cystic Fibrosis Transmembrane Conductance RegulatorNanoparticlesAnimalsCholesterolLipidsLiposomesMiceRNA, MessengerCholesterolCystic Fibrosis Transmembrane Conductance RegulatorLipid NanoparticlesLipidsLiposomesRNA, Messengercystic fibrosisinhalationlung deliverymRNA therapynebulizationpulmonary deliveryβ-sitosterol

Identifiers

PMID36038136
PMCPMC9939008
OpenAlexW4293510452

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.