Adeno-Associated Viruses as Gene Therapy Vectors

Genetic mutations in humans can be devastating in all types of organisms when those mutations negatively affect the way the organism lives within its environment. These mutated genes produce inadequate protein products, which may compromise the organism’s survivability and viability. Some common diseases that have been shown to be caused be hereditary gene mutations are breast cancer, colon cancer, Crohn’s disease, Down syndrome, Klinefelter’s syndrome, Sickle Cell disease, and many more. One way that diseases of this type are treated is through gene therapy, which is the process by which new, healthy, genes are transplanted into cells with mutated DNA using viral vectors that implant their DNA into the host’s chromosome. One particular type of virus utilized by molecular biologists is the adenovirus. Adenoviruses are non-enveloped, icosahedral, medium-sized (90-100nm), and are found in 49 immunologically distinct forms. Adenoviruses are effective as viral vectors because they can target a wide variety of cells and induce high-level gene expression of those transduced genes. Furthermore, of the 35kb that wild-type adenoviruses contain, roughly 30kb can be replaced with foreign DNA, which makes these viruses particularly plastic. Adenoviruses typically use four “early” transcriptional units that code for non-structural, regulatory, proteins, and set of “late” that code for structural proteins that make up the virus particles. These “late” genes are driven by a very strong promoter that, when bound, results in the production of a very large number of proteins. The first adenovirus vectors created had their “early” genes knocked out, which helped scientists solve two basic problems. It prevented the virus from being able to replicate, and it made room for genes to be implanted into the genome.