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ModeRN Approach to ocular disease treatment - Smart lipid-based nanoparticle systems for the delivery of mRNA to the ocular tissues

Project description

Nanoparticles for efficient ocular drug delivery

Treatment of ocular diseases most often relies on small molecule and protein drugs but is impeded by low absorption. Funded by the Marie Skłodowska-Curie Actions programme, the LIPOmRNA project aims to develop lipid-based nanoparticles (LNP) for delivering therapeutic mRNA molecules into the cornea and retina. Researchers will address anatomical barriers and optimise the technology for ocular delivery, modifying LNPs with pH-sensitive features and eye-specific surface properties. Administration of LNPs will take place through mucoadhesive eye drop formulations and intravitreal injectables to enhance retention and permeation. Project deliverables will promote the promising mRNA technology for the treatment of ocular diseases.

Objective

Many severe ocular diseases lead to visual impairment and blindness in millions of patients worldwide, and the number is rapidly growing in aging populations. Most ocular diseases are still without drug treatment and the current treatments are based on the use of small molecules and protein drugs. However, poor ocular absorption and rapid elimination restrict their development and use in ophthalmology.
Technology for mRNA transfer into the cornea and retina and subsequent expression of encoded proteins may open widely applicable possibilities for the treatment of ocular diseases (e.g. various retinal degenerations, uveitis) as topical eye drops or intravitreal injections. However, clinical application of mRNAs is limited by their poor in vivo stability and low cellular entry. Therefore, efficient and safe delivery systems for ocular mRNA transfer are urgently needed.
Our research program aims to develop lipid-based nanoparticle (LNP) systems that are specifically tailored for mRNA delivery into the corneal, conjunctival and retinal cells. The project will address the critical anatomical and physiological barriers of ocular mRNA delivery topically and intravitreally. Chemical structure and composition of LNPs will be carefully modified to optimize mRNA delivery across ocular barriers. Smart pH-sensitive LNPs with eye specific surface moieties will be used to target ocular cells and trigger mRNA release and cytosolic delivery. Moreover, eye drop formulations will be mucoadhesive, increasing precorneal residence time, whereas intravitreal injectables will be capable of permeating in the vitreous and inner limiting membrane into the retinal cells. The representative in vitro and ex vivo test models will be used to select the most promising LNPs for versatile animal experiments. Finally, in vivo pharmacokinetics and mRNA mediated anti-VEGF responses of the delivery systems will be investigated to understand their translational potential towards clinical use.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

ITA-SUOMEN YLIOPISTO
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 199 694,40
Address
YLIOPISTONRANTA 8
70211 KUOPIO
Finland

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Activity type
Higher or Secondary Education Establishments
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Total cost

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