Periodic Reporting for period 1 - LIPOmRNA (ModeRN Approach to ocular disease treatment - Smart lipid-based nanoparticle systems for the delivery of mRNA to the ocular tissues)
Période du rapport: 2023-08-01 au 2025-07-31
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 project aimed to develop lipid-based nanoparticle (LNP) systems that are specifically tailored for mRNA delivery into the corneal, conjunctival and retinal cells. The project addressed the critical anatomical and physiological barriers of ocular mRNA delivery topically and intravitreally.
The long-term goal is to create a versatile platform for RNA-based therapies that could significantly improve patient life and reduce the burden of ocular diseases.
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 project aimed to develop lipid-based nanoparticle (LNP) systems that are specifically tailored for mRNA delivery into the corneal, conjunctival and retinal cells. The project addressed the critical anatomical and physiological barriers of ocular mRNA delivery topically and intravitreally.
The long-term goal is to create a versatile platform for RNA-based therapies that could significantly improve patient life and reduce the burden of ocular diseases.
Chemical structure and composition of LNPs were designed based on FDA- and EMA-approved lipids and further improved with surface modifications to optimize mRNA delivery across ocular barriers. Over 1000 formulations were screened in vitro using retinal and corneal cell models. The most promising LNPs demonstrated up to 20-fold higher efficiency compared to benchmark system.
Using versatile animal experiments in rabbits and mice, we confirmed safety of the systems, evaluated pharmacokinetics, and estimated the systems’ efficacy. The most promising LNP showed improved retinal permeation and extended retention in the retina for more than two months after intravitreal injection. Topical administration studies revealed measurable protein expression in tear fluid, indicating successful delivery.
Using versatile animal experiments in rabbits and mice, we confirmed safety of the systems, evaluated pharmacokinetics, and estimated the systems’ efficacy. The most promising LNP showed improved retinal permeation and extended retention in the retina for more than two months after intravitreal injection. Topical administration studies revealed measurable protein expression in tear fluid, indicating successful delivery.
Being interdisciplinary, the project has contributed to various fields of science, including drug delivery, pharmaceutics and ophthalmology. The research outcomes are expected to significantly expand understanding and knowledge in the scientific community on drug delivery system development and application once published.
The development of efficient ocular mRNA transfer systems represents a remarkable innovation with potential economic, medical and societal impact. The developed technology can be combined with the emerging RNA world, thereby offering huge medical opportunities in the treatment of eye diseases.
To ensure further development, next steps include patent submission, extended animal studies, and exploration of possibilities to prolong topical residence time and enable retinal permeation across the inner limiting membrane.
The project has already attracted interest from industry, with discussions for collaboration with pharmaceutical company.
The development of efficient ocular mRNA transfer systems represents a remarkable innovation with potential economic, medical and societal impact. The developed technology can be combined with the emerging RNA world, thereby offering huge medical opportunities in the treatment of eye diseases.
To ensure further development, next steps include patent submission, extended animal studies, and exploration of possibilities to prolong topical residence time and enable retinal permeation across the inner limiting membrane.
The project has already attracted interest from industry, with discussions for collaboration with pharmaceutical company.