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Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina.

Overview

  1. Retinal Physiology and Gene Therapy Lab, Department of Neurophysiology, Institute of Physiology and Pathophysiology, University of Marburg, 35037 Marburg, Germany
  2. Department of Neurophysiology, Institute of Physiology and Pathophysiology, University of Marburg, 35037 Marburg, Germany
  3. The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3QU, UK
  4. Department of Ophthalmology, University Hospitals of Giessen and Marburg, Marburg Campus, Marburg, Germany
Journal: Molecular therapy. Nucleic acids, volume 37, issue 3, article 102996
Dates: received 26 November 2025; accepted 29 June 2026; published online 30 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.omtn.2026.102996 · PMID 42519573 · PMCID PMC13382181 · OpenAlex W4416664191
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: cellular / molecular (subfield)
Methods: Statistics
Keywords: MT: Delivery Strategies, delivery strategies, lipid nanoparticle, LNP, non-viral delivery, mRNA therapeutics, retinal degeneration, inner retina, intravitreal, subretinal, ocular therapy
Topic: RNA Interference and Gene Delivery (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: University Medical Centre Giessen und Marburg (UKGM 15/2020); Deutsche Förderprogramm für Augenheilkunde of Bayer Vital GmbH
Citations: not cited yet (Europe PMC); 60 references in the paper
Research resources: anti-Calbindin D28k RRID:AB_10841576, anti-mCherry RRID:AB_2722769, Anti-GFAP RRID:AB_305808, anti-Laminin (LAMA1 RRID:AB_477163, anti-PKCα RRID:AB_628142

Abstract

Lipid nanoparticles (LNPs) have emerged as a promising platform for retinal genetic therapy, offering a non-viral alternative to adeno-associated viruses. Although LNPs can transfect outer retinal cells, their transfection profile across inner retinal cell types remains insufficiently characterized. Here, we systematically assessed the cell-type transfection profile of conventional LNPs encapsulating chemically modified mRNA encoding mCherry in murine retinal explants, complemented by experiments in dissociated retinal cell cultures. We compared quasi-subretinal and quasi-intravitreal administrations and evaluated how retinal degeneration and inner limiting membrane (ILM) integrity influence LNP-mediated transfections. We observed that LNPs efficiently transfected Müller glia under all experimental conditions. In addition, LNPs transfected several other retinal cell types, including neurons in dissociated cells and explants, and vascular cells exclusively in explants. Subretinal delivery resulted in higher transfection rates than intravitreal administration, and overall efficiency was higher in degenerate as compared to non-degenerate healthy retinas. In healthy retinas, removal of ILM increased transfection efficiency following intravitreal administration. Together, these findings demonstrate that conventional LNPs can transfect a broader range of retinal cell types than previously recognized and highlight LNPs as a tool for mRNA delivery to the retina, with applications in gene supplementation, editing, and regenerative therapies for inner retinal disorders.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

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Data and code availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

  • Authors: added Eleonora Carpentiero (0009-0001-8513-4598); Paula Streckenbach (0009-0005-5365-6032); Vijay Renigunta (0000-0003-4123-4447); removed Eleonora Carpentiero; Paula Streckenbach; Vijay Renigunta

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 11 keywords, 2 funders, 58 references, 5 RRIDs.

Cite

This paper

Biswas, S., Carpentiero, E., Xhaferri, N., Streckenbach, P., Renigunta, V., & Lindner, M. (2026). Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina. Molecular therapy. Nucleic acids, 37(3), 102996. https://doi.org/10.1016/j.omtn.2026.102996

BibTeX

@article{biswas2026lipid,
author = {Biswas, Sumit and Carpentiero, Eleonora and Xhaferri, Nermina and Streckenbach, Paula and Renigunta, Vijay and Lindner, Moritz},
title = {{Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina}},
journal = {Molecular therapy. Nucleic acids},
year = {2026},
month = jun,
volume = {37},
number = {3},
pages = {102996},
publisher = {American Society of Gene \& Cell Therapy},
issn = {2162-2531},
doi = {10.1016/j.omtn.2026.102996},
url = {https://doi.org/10.1016/j.omtn.2026.102996},
pmid = {42519573},
pmcid = {PMC13382181}
}

RIS

TY - JOUR
AU - Biswas, Sumit
AU - Carpentiero, Eleonora
AU - Xhaferri, Nermina
AU - Streckenbach, Paula
AU - Renigunta, Vijay
AU - Lindner, Moritz
TI - Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina
T2 - Molecular therapy. Nucleic acids
J2 - Mol Ther Nucleic Acids
PY - 2026
DA - 2026/06/30
VL - 37
IS - 3
SP - 102996
SN - 2162-2531
PB - American Society of Gene & Cell Therapy
DO - 10.1016/j.omtn.2026.102996
UR - https://doi.org/10.1016/j.omtn.2026.102996
LA - en
ER -

CSL-JSON

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