AAV1-CBA-Human-SNCA-A53T

Viral vectors are highly evolved gene delivery systems for therapeutic interventions. Over the past decade, adeno-associated viruses (AAVs) have emerged as one of the most promising vectors for gene therapy and vaccines. AAV-mediated delivery of curative antivirals to sites of persistent viral infection requires the same vector optimization as conventional gene therapy, including optimization of the promoter/transgene for therapeutic expression, efficient transduction of target cells, and limiting immune responses to the vector and transgene. The simple premise of a cure for persistent viral diseases is to deliver virus-specific antivirals to inhibit, mutagenesis, or eliminate viral reservoirs within a specific anatomical site. To avoid off-target effects, high precision is required on at least two levels: specificity of target cell/tissue transduction and specificity of the antiviral for the virus rather than the host.

Gene therapy based on adeno-associated virus (AAV) vectors has achieved many successes. In 2012, the first gene therapy product was approved in Europe, Glybera, an AAV1-LDL vector for the treatment of lipoprotein lipase deficiency. Additionally, clinical trials based on AAV vectors have reported positive results for the treatment of early childhood blindness, Leber’s congenital amaurosis (LCA2), and hemophilia B. AAV-based gene delivery vectors contain an AAV capsid carrying a therapeutic transgene, with the capsid selected based on tropism for the target tissue. For example, the LCA2 trial evaluated AAV2 because of its specificity for retinal pigment epithelial (RPE) cells. AAV8, which can transduce human hepatocytes, was the choice for the hemophilia B trial, while Glybera, an AAV1-based therapeutic, targets muscle.