Evidence map›Paper›PMID 38326530›Full record

ArticlePharmaceutical research2024

Characterization of mRNA Lipid Nanoparticles by Electron Density Mapping Reconstruction: X-ray Scattering with Density from Solution Scattering (DENSS) Algorithm.

Huy M Dao, Khaled AboulFotouh, Aasim Faheem Hussain, Alexander E Marras, Keith P Johnston, Zhengrong Cui, Robert O Williams

Open access · bronzeAbstract read
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In one paragraph

Article in Pharmaceutical research, 2024. 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
3.7field-weighted citation impact, top 6% 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, 16 citations in OpenAlex.

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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

7 authors at 3 institutions in 1 country.

Huy M DaoDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA.
Khaled AboulFotouhDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA.
Aasim Faheem HussainDepartment of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Alexander E MarrasDepartment of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Keith P JohnstonMcKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Zhengrong CuiDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. zhengrong.cui@austin.utexas.edu.
Robert O WilliamsDivision of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, 78712, USA. bill.williams@austin.utexas.edu.ORCID http://orcid.org/0000-0003-4993-6427
The University of Texas at Austin · USAustin College · USWalker (United States) · US

Funding

TFF Pharmaceuticals, Inc. UTA18-000556
6 · The paper itself

Abstract

purposeThis study aimed to test the feasibility of using Small Angle X-ray Scattering (SAXS) coupled with Density from Solution Scattering (DENSS) algorithm to characterize the internal architecture of messenger RNA-containing lipid nanoparticles (mRNA-LNPs).

methodsThe DENSS algorithm was employed to construct a three-dimensional model of average individual mRNA-LNP. The reconstructed models were cross validated with cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) to assess size, morphology, and internal structure.

resultsCryo-TEM and DLS complemented SAXS, revealed a core-shell mRNA-LNP structure with electron-rich mRNA-rich region at the core, surrounded by lipids. The reconstructed model, utilizing the DENSS algorithm, effectively distinguishes mRNA and lipids via electron density mapping. Notably, DENSS accurately models the morphology of the mRNA-LNPs as an ellipsoidal shape with a "bleb" architecture or a two-compartment structure with contrasting electron densities, corresponding to mRNA-filled and empty lipid compartments, respectively. Finally, subtle changes in the LNP structure after three freeze-thaw cycles were detected by SAXS, demonstrating an increase in radius of gyration (Rg) associated with mRNA leakage.

conclusionAnalyzing SAXS profiles based on DENSS algorithm to yield a reconstructed electron density based three-dimensional model can be a useful physicochemical characterization method in the toolbox to study mRNA-LNPs and facilitate their development.

Indexed as

ElectronsLiposomesNanoparticlesLipidsRNA, MessengerRNA, Small InterferingScattering, Small AngleX-Ray DiffractionX-RaysLipid NanoparticlesLipidsLiposomesRNA, MessengerRNA, Small InterferingDENSSmRNA-LNpsSAXSsolution scattering

Identifiers

PMID38326530
OpenAlexW4391618189

What OpenQuestion holds

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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.