ISIS Neutron and Muon Source Data Journal
This is a page describing data taken during an experiment at the ISIS Neutron and Muon Source. Information about the ISIS Neutron and Muon Source can be found at https://www.isis.stfc.ac.uk.
Optimisation of peptide-LNPs for pulmonary mRNA delivery - elucidating the effect of nebulisation on the structural integrity of peptide-LNPs by neutron scattering
Abstract: mRNA therapeutics show strong potential for lung disease treatment, but their clinical use is limited by the lack of efficient delivery systems for inhalation. While lipid nanoparticles (LNPs) are the leading platform, their stability is compromised during nebulisation, leading to reduced efficacy. We previously developed a PEG12KL4 peptide that enables stable mRNA delivery post-nebulisation, but its cationic nature limits mucus penetration. In this study, we replace the PEG-lipid in LNPs with PEG12KL4 peptide to improve both mucus penetration and aerosol stability. Using a Moderna-based LNP formulation, PEG12KL4-modified LNPs (P-LNPs) maintained size after nebulisation, enhanced transfection in mucus-rich conditions, and outperformed standard LNPs post-nebulisation. The overall aim of this study is to analyse investigate the structural characteristics of the P-LNP system at various formulations and monitor the structural stability during nebulisation. The outcomes of the study would provide valuable insights that allow us to optimise and tailor a P-LNP system applicable for inhaled RNA therapy in patients with chronic lung conditions.
Principal Investigator: Dr Chien-Ming Hsieh
Experimenter: Miss Ozde Oztekiner
Experimenter: Miss Elizabeth James Pathrapankal
Experimenter: Mr Kidus Estifanos Biru
Experimenter: Professor Jayne Lawrence
Experimenter: Dr Jenny Lam
Local Contact: Dr Najet Mahmoudi
Experimenter: Dr Fabrizia Foglia
Experimenter: Mr Cheng Ma
DOI: 10.5286/ISIS.E.RB2520261
ISIS Experiment Number: RB2520261
| Part DOI | Instrument | Public release date | Download Link |
|---|---|---|---|
| 10.5286/ISIS.E.RB2520261-1 | SANS2D | 13 October 2028 | Download |
Publisher: STFC ISIS Neutron and Muon Source
Data format: RAW/Nexus
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Data Citation
The recommended format for citing this dataset in a research
publication is as:
[author], [date], [title], [publisher],
[doi]
For Example:
Dr Chien-Ming Hsieh et al; (2025): Optimisation of peptide-LNPs for pulmonary mRNA delivery - elucidating the effect of nebulisation on the structural integrity of peptide-LNPs by neutron scattering, STFC ISIS Neutron and Muon Source, https://doi.org/10.5286/ISIS.E.RB2520261
Data is released under the CC-BY-4.0 license.
