Syn-GFP AAV (Serotype BR1)

One particular parvovirus, AAV, has been intensively studied for its attractiveness as a gene therapy vector. AAV has a range of properties that make it a promising vector for clinical gene therapy applications, and to date, more than two hundred clinical trials have used AAV as a gene delivery vector. AAV is able to infect both dividing and non-dividing cells, enabling gene delivery to both circulating cells (e.g., hepatocytes) as well as terminally differentiated cells (e.g., neurons) that are typically inaccessible to gene delivery by other methods. In addition, AAV does not generally induce a strong immune response, thereby reducing the risk of adverse immune responses (e.g., cytokine storms). Furthermore, in recombinant form, AAV rarely integrates into the host genome, although AAV-delivered DNA can persist in an episomal state for long periods of time, allowing for long-term expression of therapeutic transgenes. Furthermore, AAV lacks any known pathogenicity, suggesting that the use of AAV as a gene delivery vector has a superior safety profile.

The only requirements for packaging DNA into the AAV capsid are the presence of flanking ITRs and that the genome size must not exceed ~5 kb. Therefore, any genetic material that meets these requirements can be delivered using rAAV vectors. These properties, combined with the known range of AAV serotypes, allow for the targeted delivery of specific genetic material to desired target tissues while maintaining a good safety profile and reducing off-target delivery of transgenes. It is for these reasons that AAV has been widely explored for use as a gene therapy vector. In summary, the results of clinical trials that have been conducted or are ongoing with AAV vectors continue to demonstrate that rAAV vectors have an excellent safety profile. In addition, many successful clinical trials utilizing AAV have been conducted to deliver genes to various organs. For example, multiple AAV gene therapy trials are ongoing aimed at treating various diseases of the central nervous system (CNS). In addition, many trials have been conducted aimed at delivering factor VIII or factor IX to the liver to treat hemophilia A or hemophilia B, respectively, with promising results.