Lipid nanoparticles enable mRNA delivery to diverse cell types of the inner Retina.
Overview
- Retinal Physiology and Gene Therapy Lab, Department of Neurophysiology, Institute of Physiology and Pathophysiology, University of Marburg, 35037 Marburg, Germany
- Department of Neurophysiology, Institute of Physiology and Pathophysiology, University of Marburg, 35037 Marburg, Germany
- The Nuffield Laboratory of Ophthalmology, Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3QU, UK
- Department of Ophthalmology, University Hospitals of Giessen and Marburg, Marburg Campus, Marburg, Germany
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.
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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://
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/
url = {https://
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/
VL - 37
IS - 3
SP - 102996
SN - 2162-2531
PB - American Society of Gene & Cell Therapy
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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