Adeno-associated virus serotypes 1-6 were discovered in the 1960s. There was no new AAV serotype isolated in the past 30-40 years. The novel AAV serotypes, AAV7 and AAV8, which we reported in the paper, were the first AAVs that were isolated by a molecular rescue method and demonstrated superb gene transfer efficiency as gene transfer vectors in liver (10- to 100-fold more efficient than any other AAV vectors).

Our paper described both a new discovery of novel AAVs as potent gene transfer vectors and a new methodology for isolating new viruses as molecular clones. This is very different from the classic strategy of virology, which focuses on isolates of infectious viruses. Here we targeted for molecular isolates the part of a viral chromosome that is responsible for serological reactivity and tissue tropism.

AAV-based vectors hold promises as the vector of choice for many different gene therapy applications. However, use of AAV1-6 based vectors for a liver-directed gene therapy might be hindered by the deficiency of those vectors to deliver genes to the liver to achieve therapeutic outcomes. With 10- to 100-fold enhancement in targeting liver cells by AAV7 and 8 vectors which we described in the paper, it should now be a time of more vigorous development of pre-clinical and clinical gene therapy protocols, both for AAV-mediated and liver-directed gene therapy applications—such as the potential treatment of clotting factor disorders (Hemophilia A and B), familial hypercholesterolemia, and other liver diseases. In addition, the high biological potency of AAV7- and 8-based vectors should be very helpful in a reduction of the dose regimen needed to achieve therapeutic effect, resulting in less vector-related toxicity and vector demands for AAV manufacturing which has been a major challenge to this field of research.

I am an associate of Dr. Wilson's and have been responsible for novel AAV discovery and vector development in his group.