mRNA-Based Therapy for Ocular Diseases

mRNA-Based Therapy for Ocular Diseases

In recent years, nucleic acid-based therapeutics (including mRNA-based therapeutics) have attracted increasing attention for the treatment of ophthalmic pathologies. Advances in mRNA technology have promoted gene delivery in hard-to-transfect retinal cells, further for intracellular gene silencing, genome editing and so on. mRNA not only provides rapid and transient protein expression but also avoids the risk of genomic integration due to no necessity for nuclear entry. The use of viral vectors has the disadvantage of immunogenic response and long-term toxicity. Lipid-based nanoparticles (LNPs), one of the non-viral vectors, have shown excellent clinical efficacy as well as safety, and are easy to scale up. Therefore, LNPs-based mRNA presents an excellent opportunity for the treatment of numerous genetic disorders affecting the different layers of the retina.

Gene-based therapy for ocular diseases

In recent years, more and more preclinical and clinical studies have been conducted to evaluate gene therapy for ocular diseases, including atrophic macular degeneration, myopia, and inherited retinal degeneration. For instance, in 2017, subretinal AAV delivery for ocular gene therapy received FDA approval, highlighting the potential of gene-based therapy for eye disorders. For the gene-based treatment of the retina, clinicians and scientists have debated the use of subretinal injections, which can lead to the visual impact of detaching the fovea or a fragile degenerating retina. As an alternative approach for the subretinal injections, the intravitreal injection does not damage and detach the retina, providing a safer ocular route for gene delivery. The vitreous humor is composed of various proteins which restrict diffusion (such as collagen, hyaluronan, glycosaminoglycans) and an inner limiting membrane (ILM). To achieve successful nucleic acid delivery to the retina, several barriers should be considered, including the barrier to the vitreous humor, the neural retina and the RPE.

The development of lipid-based nanoparticles for mRNA delivery to the retina

At present, there is an urgent need for the development of non-viral gene delivery vehicles for the retina. Due to packaging capacity, immune response problems and cost, the ability of viral vectors to treat different genetic forms of retinal degeneration are limited. Lipid nanoparticles are at the forefront of non-viral gene therapy. A previous study tested the ability of eleven different LNP variants to encapsulate mRNA and deliver it to the back of the eye. It is reported that LNPs contained ionizable lipids with unsaturated hydrocarbon tails showed the highest amount of mRNA delivery to the retina. Moreover, researchers have generated several novel LNPs with different PEG content. Subretinal injections of LNP-mRNA encoding luciferase shown that LNPs with 0.5% PEG content elicit the highest expression. The gene delivery shows cell-type specific, with high expression in the retinal pigmented epithelium (RPE) and low expression in the Müller glia. In general, LNP-delivered mRNA can be applied for the treatment of monogenic retinal degenerative disorders of the RPE, direct retinal reprogramming or genome editing.

Lipid nanoparticles for delivery of messenger RNA to the back of the eye.Fig 1. Lipid nanoparticles for delivery of messenger RNA to the back of the eye. (Patel, S., et al, 2019)

In addition, an intravitreal delivery method and a series of intravitreal nanoparticles have been developed to treat ocular diseases, such as glaucoma, inflammation, angiogenesis, and retinal degeneration. To develop intravitreal nanoparticles, four main parameters should be considered, including size, charge, stability, and ligands, which continuously affect their intraocular distribution and elimination. The development of these LNPs based on the route of subretinal and intravitreal delivery will greatly expand the utility of LNP-mediated mRNA therapies for the eye.

If you have any requirements in this area, please don't hesitate to contact us. Creative Biogene is a leading service provider in mRNA-based drug research and development. Our extensive experience, an excellent team of experts, and advanced technology platforms make us an ideal partner for worldwide customers. According to the desired applications, we can support our customers with the most affordable, high-quality custom mRNAs and mRNA delivery systems.


  1. Patel, S., et al. (2019). "Lipid nanoparticles for delivery of messenger RNA to the back of the eye." Journal of Controlled Release, 303, 91-100.
  2. Ryals, R. C., et al. (2020). "The effects of PEGylation on LNP based mRNA delivery to the eye." Plos one, 15(10), e0241006.

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