Adeno-Associated Viral Vectors (AAVs) for Therapeutic Development

AAV is ideally suited for many molecular therapy applications, as it is:

• Non-pathogenic
• Delivers genes to dividing and non-dividing cells
• Gives long-term, stable gene expression

Electron micrograph of purified AAV
(courtesy P. Bell, University of Pennsylvania)

Two major factors drove the search for the novel AAV serotypes that form the basis for ReGenX AAV Vector Technology:

• Existing AAVs, although useful, were not efficient at transducing many major tissue targets in vivo.
• Humans have a relatively high frequency of pre-existing neutralizing antibodies to existing AAVs, which can dramatically curtail the efficiency of transduction.

To circumvent these limitations, new AAV capsid sequences were isolated from human and non-human primate tissues, cloned to generate recombinant AAV vectors, and characterized in multiple tissues in vivo. The resulting ReGenX AAV Vector Technology, proprietary AAV serotypes, including those identified as AAV7, AAV8 and AAV9, stood out by virtue of being 1–2 logs more efficient than AAV2 in delivering genes to mouse liver. The ReGenX AAV Vector Technology has also demonstrated enhanced transduction of other, selected tissues. Many of these serotypes have a lower frequency and lower titers of neutralizing antibodies as compared with AAV2¹.

A third limitation of working with AAV vectors has been difficulty in manufacturing the amounts of AAV required for human therapeutic applications. The ReGenX AAV Vector Technology has included development of improved manufacturing that should allow for efficient, high-titer production of vector. Whether the transgene is used for therapeutic effect or biological systems research, ReGenX AAV Vector Technology can deliver the performance needed for many applications. ReGenX’s ongoing research and development is further improving gene transfer vector technology and we are working with customers and partners to increase vector effectiveness for their research as well as their therapeutic goals.