Nonviral mRNA gene therapy for retinal diseases

Gene therapy is an exciting therapeutic option with the potential to cure an increasing number of genetic diseases. Ophthalmology has been at the forefront of this innovative field, with one ocular gene therapy already receiving FDA and EMA approval. However, challenges such as high costs, immune responses, and potential long-term toxicity of viral vectors remain significant roadblocks to clinical translation. 

Our lab is committed to addressing these obstacles by combining in vitro transcribed mRNA and nonviral delivery systems to target inherited retinal diseases (IRDs). As highlighted in our opinion article published in Trends in Molecular Medicine, it is crucial to develop novel approaches that not only match the efficacy of viral gene therapies but also prioritize safety and affordability. By leveraging advancements in nanotechnology and mRNA, we aim to make retinal gene therapies safer and accessible to a wider patient population, particularly in low- and middle-income countries. 

Launched in 2022, our ongoing project evaluates the feasibility of delivering synthetic mRNA encapsulated in lipid nanoparticles to the retina, employing gene supplementation in cellular and mouse models of Choroideremia as a proof-of-concept (learn about our in vitro models of Choroideremia). To start, we are interested in assessing the toxicitiy and inflammatory potential of this approach, along with its transfection efficiency, durability of expression, and retinal penetration capacity. Once we optimize these parameters, we aim to customize the mRNA cargo for gene supplementation therapies in other recessive IRDs and investigate the encoding of genome editing tools, thereby estabilishing a versatile platform for addressing various hereditary retinopathies. 

Period: 2022 - Ongoing

Funding: Champalimaud Foundation