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The technology is a novel, plasmid-free manufacturing system for robust and reproducible manufacture of AAV at scale.
UK-based biotechnology company Oxgene announced on Sept. 22, 2020 the launch of TESSA, a scalable, plasmid-free manufacturing system for adeno-associated virus (AAV). The technology addresses industry-wide challenges associated with robust and reproducible AAV manufacture at scale, such as high cost of goods and low packaging efficiency, according to a company press release.
AAV is considered a popular choice of viral vector to deliver gene therapies to patients because of its low immunogenicity, favorable safety profile, and the ease with which it transduces numerous cell types and tissue types. Manufacturing systems have not kept pace with biological advances, however, resulting in costly gene therapies that are difficult to produce at scale and that are subject to inherent batch-to-batch variability. This poses a serious challenge to regulators and health authorities when reviewing these treatments for approval in clinical use.
The TESSA technology overcomes manufacturing obstacles by taking advantage of AAV’s natural relationship with adenovirus. Adenovirus, with which AAV naturally co-exists, provides the “help” that AAV needs to replicate, but the downside is that the adenovirus replicates itself as well as the AAV, leading to high levels of adenoviral contamination if this process is translated to an industrial context, the company said in the press release.
Oxgene addressed these challenges by manipulating the adenoviral life cycle to provide high quality help for AAV replication but without replicating itself, thus reducing adenoviral contamination by 99.9999% in a manufacturing run. Integration of the AAV rep and cap genes into the adenoviral vector keeps everything required for AAV production, except the AAV genome, in a single viral vector. The AAV genome can either be encoded within a second TESSA vector, in a plasmid, or within an AAV particle itself. By using two TESSA vectors, yields of AAV2 can be improved by 40-fold, accompanied by a 2000-fold increase in particle infectivity compared to a standard three-plasmid manufacturing approach.
Once the first AAV seed stock is produced, co-infecting cells with this AAV alongside another TESSA vector can then 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. 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,” said OXGENE CEO Dr. Ryan Cawood in the press release.