AAV5-CAG-FLPo

From the moment gene therapy was first hypothesized as a potential treatment for disease, the search for the perfect gene vector has been on. To be a successful therapeutic candidate, an ideal gene vector must have high gene transfer rates, produce long-term gene expression, and have low immunogenicity and pathogenicity. Replication-deficient retroviruses were the original vectors used in the early stages of gene therapy. However, potential genotoxicity resulting from integration into the host genome raised concerns that hampered progress.

The second wave of gene therapy in the early 21st century was marked by the increased use of AAV. AAV meets essentially all of the characteristics required for a successful gene vector. Although complex immune responses to AAV-based gene therapies are known to occur, overall AAV maintains an impressive safety and tolerability profile. Furthermore, in many cases, AAV can effectively transduce both non-dividing and dividing cell types within clinically relevant time periods. While AAV2 is the most widely used variant because it was the first serotype discovered, there are many other serotypes with different tropisms that give AAV a wide range of clinical applicability. Combined with these characteristics, AAV has become the vector of choice for gene therapy research with the highest success rates.