New nanoparticle gene therapy research provides hope for treating inherited sight loss
Researchers from Ghent University have published a study that has the potential to transform inherited retinal disease (IRD) treatment development.
Most gene therapies for IRDs work on the premise of delivering an entire new gene to replace the mutated one via a viral vector. This is a small virus, that doesn’t cause illness in humans, which is used as a delivery system to package and transport the gene therapy into cells to alter the genetic material.
However, it is a long-established issue within treatment development that inherited retinal conditions can be caused by mutations in very large genes. For example, Stargardt disease is most often caused by mutations in the ABCA4 gene, which is made up of around 128,000 base pairs and produces a protein made up of 2273 amino acids. This ABCA4 gene, like many others identified as causative genes for IRDs, is too large to fit inside one viral vector.
This latest research by the team at Ghent University in Belgium, has shown encouraging results for the use of lipid nanoparticles as delivery systems rather than viral vectors, overcoming the size barrier that has long-been an issue in IRD research.
Lipid nanoparticles, also known as LNPs, are tiny fat-like particles that are able to carry large genes into cells. They are made up of several different fats known as lipids, each with a specific role to play. This combination of lipids gives structure and stability to the molecules, allowing for both the carrying and release of their ‘cargo’ (large genes) into cells. LNPs also shield delicate molecules like RNA that get broken down quickly in the body and are small enough to pass through cell membranes easily.
A large gene known to cause Retinitis Pigmentosa (RP) is EYS, made up of 2,000,000 base pairs and producing a protein made up of 3145 amino acids. Scientists were able to show that when the EYS gene was loaded into LNPs the full-length gene was successfully delivered into retinal cells and able to make the correct RNA needed for normal protein production. This study was conducted in cultured retinal cells and retinal tissue from cows. Please note that this research is currently at a preclinical level and has not yet been tested in humans.
With many IRDs being caused by large genes that are unsuitable for traditional delivery methods such as viral vectors, this is a huge step forward in research, potentially expanding the possibility of treatments to IRDs that weren’t considered feasible for treatment development before.