Oxgene, a biotechnology company designing and developing scalable gene therapy technologies, has launched its scalable, plasmid-free manufacturing system for AAV. The new TESSA technology addresses industry-wide challenges associated with robust and reproducible AAV manufacture at scale, according to Oxgene. These include high cost of goods, and low packaging efficiency. TESSA aims to deliver a paradigm shift in scalable AAV manufacture.
 
Adeno-associated virus, or AAV, is a popular choice of viral vector to deliver gene therapies to patients, owing to its low immunogenicity, favorable safety profile and the ease with which it transduces numerous cell and tissue types. However, manufacturing systems have not kept pace with biological advances, leaving these therapies costly, difficult to produce at scale, and subject to inherent batch-to-batch variability. This represents a challenge to regulators and health authorities when it comes to approving these treatments for clinical use.
 
Oxgene says its TESSA technology overcomes manufacturing obstacles by taking advantage of AAV’s natural relationship with another virus—the adenovirus. In nature, AAV co-exists with adenovirus, which provides the ‘help’ AAV needs to replicate. However, as well as replicating the AAV, the adenovirus also replicates itself, leading to high levels of adenoviral contamination if this process is translated to an industrial context.
 
Oxgene has addressed these challenges by manipulating the adenoviral life cycle so that it can still provide high quality help for AAV replication, but is unable to manufacture itself, reducing adenoviral contamination by 99.9999% in a manufacturing run. Integration of the AAV rep and cap genes into the adenoviral vector means that everything required for AAV production, except the AAV genome, can be provided in a single viral vector. Meanwhile, the AAV genome can either be encoded within a second TESSA vector, in a plasmid, or within an AAV particle itself. Using two TESSA vectors improves yields of AAV2 by 40-fold, accompanied by a 2000-fold increase in particle infectivity compared to a standard three-plasmid manufacturing approach.
 
Once this first AAV seed stock has been produced, co-infecting cells with this AAV alongside another TESSA vector can further amplify the AAV in a simple, reproducible and scalable manner, removing the reliance on expensive and limiting plasmids for AAV manufacture.
 
“The gene therapy industry’s reliance on plasmids is a major limitation for robust and reproducible large-scale AAV manufacture,” said Ryan Cawood, chief executive officer, Oxgene. “By taking a ‘back to nature’ approach to rethink AAV production from the ground up, we’ve developed a truly innovative new technology that we expect to transform the way AAV is manufactured. By combining high AAV yields with scalability, packaging efficiency and increased infectivity, we hope that TESSA technology will help to bring down the overall cost of goods involved in gene therapy development. We hope it will also improve the safety of the final therapeutics, as the higher quality, more infectious AAV resulting from TESSA based manufacture could mean significantly lower effective doses.”
 
Oxgene has so far developed and validated TESSA vectors for AAV2, 5, 6 and 9 and is now taking requests for service projects and product pre-orders to further develop and evaluate this technology.