Voretigene neparvovec

Voretigene Neparvovec-rzyl (VN-rzyl) is an adeno-associated virus vector-based gene therapy. An adeno-associated virus is a small virus that infects humans and other primates. It is not pathogenic and it causes a very mild immune response. This type of virus is vastly used as vectors for gene therapy because they can infect dividing and quiescent cell integrating just the carried genes into the host genome without fully integrating into the genome. An advantage of this adeno-associated virus is the high predictability, unlike retrovirus, as they associate with a specific region of the human cellular genome localized in the chromosome 19. When used in genetic therapy, this virus is modified for the elimination of its negligible integrative capacity by the removal of rep and cap and the insertion of the desired gene with its promoter between the inverted terminal repeats. VN-rzyl was developed by Spark Therapeutics Inc. and FDA approved on December 19, 2017.

VN-rzyl is indicated for the treatment of children and adult patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. The administration of VN-rzyl is conditioned to the physician determination of the presence of viable retinal cells. The RPE65 represents the LCA2 form of the Leber's congenital amaurosis (LCA). LCA is a group of inherited conditionts that involves retinal degeneration and severe vision loss in early childhood leading to total blindness by 30-40 years old. The LCA2 form is associated with a mutation that interferes with the isomerohydrolase activity of the retinal pigment epithelium. The isomerohydrolase activity transforms the trans-retinyl esters to 11-cis-retinal which is the natural ligand and chromophore of the opsins of rod and cones photoreceptors. In the presence of RPE65 mutations, the opsins cannot capture light or transduce it into electrical responses to initiate vision.

• Hepatitis B Virus (HBV)