AI Article Synopsis
- Ocular delivery of lipid nanoparticles (LNPs) containing mRNA facilitates gene delivery and editing for potential treatments related to blindness.
- Different LNP variants, such as LNPa, LNPx, and LNPz, show varying efficacy in transfecting retinal cells, with LNPx demonstrating significant distribution across photoreceptors and the retinal pigmented epithelium (RPE).
- LNPs modified with PEG variants can influence how effectively mRNA is taken up by specific retinal cells, paving the way for future gene editing to correct genetic mutations associated with vision loss.
Article Abstract
Ocular delivery of lipid nanoparticle (LNPs) packaged mRNA can enable efficient gene delivery and editing. We generated LNP variants through the inclusion of positively charged-amine-modified polyethylene glycol (PEG)-lipids (LNPa), negatively charged-carboxyl-(LNPz) and carboxy-ester (LNPx) modified PEG-lipids, and neutral unmodified PEG-lipids (LNP). Subretinal injections of LNPa containing Cre mRNA in the mouse show tdTomato signal in the retinal pigmented epithelium (RPE) like conventional LNPs. Unexpectedly, LNPx and LNPz show 27% and 16% photoreceptor transfection, respectively, with striking localization extending from the photoreceptor synaptic pedicle to the outer segments, displaying pan-retinal distribution in the photoreceptors and RPE. LNPx containing Cas9 mRNA and sgAi9 leads to the formation of an oval elongated structure with a neutral charge resulting in 16.4% editing restricted to RPE. Surface modifications of LNPs with PEG variants can alter cellular tropism of mRNA. LNPs enable genome editing in the retina and in the future can be used to correct genetic mutations that lead to blindness.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575971 | PMC |
| http://dx.doi.org/10.1038/s41467-023-42189-3 | DOI Listing |
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