Molecular design of nanovesicles for protein-replacement in retinal dystrophy therapeutics

Retinal dystrophies are a heterogeneous group of genetic diseases, which affect photoreceptors, the retinal cells responsible for triggering vision, causing progressive blindness. One form of retinal dystrophy, cone dystrophy, is caused by genetic defects in the gene responsible for the production of GCAP1 protein. This protein is a neuronal sensor, which detects calcium inside the cell thus regulating important biological processes. Genetic defects cause an alteration of GCAP1 function and perturb the biological processes regulated by the protein, thus triggering photoreceptor degeneration. No effective therapy for the treatment of retinal dystrophies exists, therefore a number of novel nanomedicine approaches are currently under investigation, which include the use of small lipid vesicles, liposomes, to encapsulate drugs and transport them to final release site. Liposomes have been shown to reduce drug toxicity and increase the residence time of active molecules in the eye, moreover they can effectively protect their content from premature degradation.

GOALS

  • Probing liposome capability to deliver functional GCAP1 to retinal photoreceptors, for functional protein replacement in patients affected by cone dystrophy
  • Optimization of liposome composition and encapsulation strategies
  • Assessment of thermal and chemical stability of GCAP1-loaded liposomes for storage and protein administration
  • Biochemical assays to probe the functionality of the released protein.

funding

This project is supported by Verona Brain Research foundation