BIOCHEMISTRY, BIOMEDICINE & PHARMACEUTICS

Adeno associated virus (AAV) is a naturally occurring single-stranded DNA virus that belongs to the parvovirus family. The commonly used viral vectors for gene therapy are derived from naturally occurring AAVs. These vectors are genetically modified/engineered that do not contain and devoid of genes encoding viral proteins critical for their viral replication. The viral gene is replaced with the transgene of interest is packaged into the AAV viral capsid and administration to humans. The AAV viral vectors enable attachment and entry of transgene into the target cells. Once inside the cell nucleus, the transgene remains in the episomal form and expresses the gene of interest. Although recent evidence has shown that long-term stable expression of these transgenes can be achieved in pre-clinical models and humans, there is inherent immunogenicity risk associated with adeno-associated vectors which include: -Pre-existing antibodies and T cell response against viral vectors -Neutralizing an...

What are Hemophilia disorders ? Hemophilia is the group of bleeding disorders that are caused by a deficiency of proteins (factors) of the blood clotting cascade. Hemophilia A is caused by the deficiency of factor VIII protein and Hemophilia B is caused by a downstream protein factor IX. The deficiency of the factors VIII and IX affect the clotting cascade, resulting in higher and spontaneous bleeding episodes. The severe bleeding disorder leads to spontaneous bleeding in joints and soft tissue resulting in arthropathy; and increased risk of intravascular and intracranial hemorrhage. Why the development of new treatment paradigm is necessary? The standard treatment for hemophilia (A and B type) is the intravenous infusion of an exogenous clotting protein more than once a week to prevent bleeding. In addition, the development of inhibitors decreases the efficacy of the exogenous replacement factor and the severe hemophilia patients do not respond to these therapies.  There...

Inherited Biallelic RPE65 Mutation-Associated Retinal Dystrophy Inherited retinal dystrophies are a group of rare blinding conditions that are associated with progressive visual dysfunction. This rare genetic disorder is classified based on the phenotype, and the mutation in any one of more than 220 different genes are causal for this rare blinding condition. Retinitis pigmentosa is the most common subgroup of inherited retinal dystrophy characterized by reduced ability to perceive light and progressive loss of visual field. RP is genetically heterogeneous, and mutations in any one of over one hundred genes can cause the phenotype. RPE65 gene encodes all-trans-retinyl ester isomerase, an enzyme crucial to the retinoid cycle Autosomal recessive biallelic mutations in this gene lead to the inability to regenerate 11-cis-retinal, via 11-cis-retinol, in the retinal pigment epithelial cells RPE cells. This impairs the ability of RPE cells to respond to light, which disrupts the vis...