LysoSENS: a synthetic biology approach to treat age-related macular degeneration - Lorenzo Albanello

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Author: Lorenzo Albanello - SENS Foundation Research Center

A2E is a toxic compound that is formed in the lysosomes of retinal pigment epithelial (RPE) cells, as a normal by-product of the vitamin A metabolism that is essential for photoreceptor activity. It is a major component of RPE lipofuscin, which is thought to mediate light-induced oxidative damage associated with aging due to its photosensitive nature; its presence leads to the formation of epoxides that are even more toxic to the host cell. I'm studying the potential of enzyme replacement strategies to help the RPE get rid of A2E, breaking it down into less toxic catabolic products. This can be achieved in two ways: either by systemically delivering particular enzymes that are engineered to target a receptor that will cause those enzymes to be endocytosed and directed into the cells' lysosomes; or by using a gene therapy approach to enable the RPE to degrade A2E autonomously. Both approaches are being investigated by the LysoSENS project, which is now using novel methods for gene assembly to accelerate our research, giving us the ability to study our therapeutic strategies in medium-throughput assays in cultured RPE cells.