Voretigene neparvovec

VN-rzyl is designed for the delivery, in the cells of the retina, of a normal copy of the gene encoding for the human retinal pigment epithelial protein whose molecular weight is 65 kDa. The delivery of this gene will allow the production of the RPE65 protein re-establishing the visual cycle and restoring the visual function. The adeno-associated viral vectors (AAVV) presents two open reading frames encoding for its replication (rep) and capsid (cap). It contains as well a zone with inverted terminal repeats which are required for the replication and packing of the viral genome. The replication of the AAVV requires the presence of a co-infector such as adenovirus or herpesvirus. Thus, without this co-infector, AAVV stays latent with its viral genome in the infected cell. The AAVV construct will contain the transgene in the inverted terminal repeats and it will replace the rep and cap sequences. The final AAVV will enter the cell nucleus and persist in different states. The first one involves the conversion of the AAVV genome into double-stranded circular episome which will later become a concatamer and provide a long-term transgene expression, particularly in non-dividing cells. The second option, presented in 0.1% of AAVV, is the integration at non-homologous sites of the host genome as single-copy proviruses or concatamers. In both options, there will be the presence of transgene expression.