Liposomes as biocompatible carriers of genes, proteins and small molecules
Inherited retinal diseases (IRDs) lead to the progressive death of photoreceptors in the retina. In cone-rod dystrophy (CORD) visual acuity and colour-discrimination are lost first, followed by dim light vision. Conversely, in retinitis pigmentosa (RP) dim light vision is initially compromised. No effective cure exists for RP and CORD except for gene therapy carried by viral vectors and limited to some specific forms of disease. We will design innovative nano-sized lipid vesicles and test their effectiveness as vehicles to deliver genes, small molecules or high amount of proteins with the potential to slow down or stop retinal degeneration. Vision loss remains one of the most dreaded diseases of the nervous system due to its dramatic impact on the quality of life of affected patients. Many early-onset forms of IRD are caused by inherited mutations in key genes involved in the light transduction process in photoreceptors, which lead to legal blindness and are currently incurable. Biocompatible lipid nanovesicles, which offer a variety of administration routes and low adverse effects, can contain high amounts of therapeutic genes, small molecules or proteins, and thus have great potential to improve the currently limited therapeutic options for both RP and CORD.
GOALS
We will:
create small carriers called liposomes that have a fully biocompatible chemical composition an no viral component, therefore lacking potential adverse effects. We have previously found that these liposomes naturally fuse with the membrane of photoreceptor cells and release their content in functionally relevant amounts.
directly measure the effects of the administration of the newly designed vesicles in suitable cellular and animal models of IRD
Either of three types of molecules will be encapsulated into liposomes:
a) large amounts of functional proteins to replace those that are mutated and thus defective in the patients;
b) a functional gene that can incorporate in the photoreceptor machinery and produce the healthy form of the mutated protein;
c) small molecules with proven therapeutic activity.
