Discover TESSA® for Scalable AAV Production

The proprietary TESSA® (Tetracycline enabled self-silencing adenovirus) technology delivers high titer and high quality AAV to gene therapy pioneers. Our team engineers TESSA® vectors to encode your gene or capsid of interest for high quality manufacture of AAV. The result is an easily scalable, contaminant-, chemical- and transfection- free technology.

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Key Benefits of TESSA®

Overcome typical challenges in scale and costs
to meet market demand.

Better Yield

Higher Quality

Improved Safety

Lower Costs

Greater Scalability

Accelerated Timelines

Who Needs TESSA®?

Anyone who needs to produce a large amount of AAV to adequately meet patient demands or are targeting indications that require high doses of AAV can gain from the application of TESSA® technology. In addition, developers who are facing challenges related to the cost of production or struggling to meet quality or yield targets may also want to evaluate TESSA®.
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How TESSA® Works

wuxi advanced therapies tessa aav scalable production

The Science Behind It

TESSA® vectors take advantage of the adenoviral lifecycle, which contains two temporal phases: early and late. The early phase provides all the adenoviral help needed for high fidelity, high titer AAV manufacture. The late phase leads to adenovirus contamination.

We’ve engineered supremely tight regulation of the adenoviral late region, which is wholly responsible for producing adenovirus structural proteins. Using TESSA® technology, full early region expression, which provides all the help needed for AAV production, is enabled. However, the late region gene expression is turned off, meaning there is no adenoviral structural protein production.

This tightly represses adenovirus production during an AAV manufacturing run, while increasing recombinant AAV (AAV) yield, packaging efficiency and infectivity compared to both Ad5 helper plasmid or wild-type adenovirus. Stable integration of AAV Rep and AAV Cap into the TESSA® vector allows efficient and simultaneous delivery of all the necessary components for AAV replication in a single agent.

wuxi advanced therapies tessa aav two different models

Two Different Approaches

TESSA® vectors can be combined in two different ways to produce AAV. The process variation between the two approaches is the method by which the gene of interest (GOI) is introduced. A TESSA® vector encoding Rep and Cap can be combined with either a TESSA® vector (TESSA® Duo model) or an AAV encoding the GOI (TESSA® Pro model.)

wuxi advanced therapies tessa aav increased yield

Increased Yields

We observe an increase in AAV2 infectious yield where 1 in 23 genomes containing AAV2 particles is infectious from TESSA® , compared to 1 in 186 from plasmid-based system. Producing AAV2 using TESSA® Duo (two TESSA® vectors) results in ~43-fold total increase in AAV particle yields compared to the 3-plasmid system. The full power of TESSA® is realized through the combination of the percentage full improvement (left) with the upstream yield improvement. For AAV6-EGFP & AAV2-EGFP, this has meant a 31.4-fold & 42.9-fold higher yield than that achieved using the 3-plasmid system. We also see an increased percentage of full capsids from 73% up to 95%.

wuxi advanced therapies tessa aav negative feedback loop

Negative Feedback Loop

A Tet repressor (TetR) binding site is inserted into the Major late promoter, while the TetR gene itself is encoded within the late region. This creates a negative feedback loop, where adenoviral structural proteins can only be produced in the presence of doxycycline.

wuxi advanced therapies tessa aav scalable manufacturing

Scalable Manufacturing

Using two TESSA® vectors (Duo) to produce AAV6 in a 50L bioreactor results in a 10-fold improvement in the AAV6 yield compared the 3-plasmid system. Consistent AAV2 yields across a range of production scales (125mL-200L) demonstrate the scalability of manufacturing using TESSA®.

wuxi advanced therapies tessa aav packaging efficiency

Packaging Efficiency

Top: The gene of interest (GOI) is packaged more efficiently into AAV made using TESSA® Duo and this results in a higher percentage of particles containing the full sequence of the GOI (full particles). AAV6- EGFP produced using TESSA® Duo at 200L scale had 26% more full particles than those produced using the 3- plasmid system.

Bottom left: This higher percentage of full particles appear lighter when negative stained and visualized using electron microscopy. Bottom right: This higher percentage full particles is enriched in the post drug substance, which contains 94.4% full particles. Scale bar = 200nm.

wuxi advanced therapies tessa aav particle quality

Particle Quality

AAV2 produced using TESSA® Duo (blue) contains significantly more infectious particles (1 in 23) than those made using the 3-plasmid system (1 in 186) (grey). As seen on the right, a higher number of infectious particles translates to greater transduction efficiency, as demonstrated by the relative expression levels of EGFP in HEK293 & U87 cell lines.

wuxi advanced therapies tessa aav reduced costs

Reduced Costs

Large scale manufacturing of AAV using TESSA® technology eliminates the need for costly starting materials. It’s ideally suited for rapid and robust production of GMP quality AAV, using the same batch of TESSA® starting material for multiple runs reduces the potential for batch-to-batch variation. Ultimately, TESSA® technology will result in economic benefits whilst improving the safety of AAV gene therapies.

The Path to Drug Production
with TESSA®

Evaluation Services

DIY Demo and Evaluation Kits

Custom Production

AAV Vector Release Package

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How long will an evaluation project take?

What kind of support is providing during our DIY evaluation??

What is the stability of TESSA® vector stocks?

Is it cheaper for us to produce AAV using the TESSA® Pro process over the plasmid system? and at what scale of production is this true?

Which AAV serotype does the rep gene come from?

Can we use a custom capsid with TESSA® technology?

I have more questions, what is the best way to find the answers?

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