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TESSA™: Scalable AAV Production

Scalable, contaminant and transfection free AAV production using proprietary self-silencing adenoviral vectors.

TESSA™ Vector Engineering

Our proprietary self-silencing adenoviral vectors deliver high titre, high quality AAV. We can engineer TESSA™ vectors to encode your gene or capsid of interest for high quality manufacture of AAV seed stocks.

Process Development

We optimise processes for pre-clinical manufacture of gene therapy vectors in our ISO:9001 accredited lab. We manufacture up to 10L scale before assisting technology transfer to your own facilities or CMO.

Evaluate and License

Our revolutionary TESSA™ technology and GMP banked suspension clonal HEK293 cell line are now available for evaluation.

TESSA™ technology represents a paradigm shift in AAV manufacturing

Ryan Cawood, Chief Executive at OXGENE

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Tetracycline enabled self silencing adenovirus (TESSA™) technology

TESSA™ vectors deliver    a step-change in AAV manufacture; an easily scalable, contaminant-, chemical- and  transfection free technology. 

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 titre 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  still enabled, but  the    late region gene expression is turned off, meaning there is no adenoviral structural protein    production. This represses adenovirus production by 99.99999 -100%  during an AAV manufacturing run, while increasing rAAV 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. 

How it works

There are two stages to AAV manufacture with TESSA™. The first is to produce initial AAV seed stock.  This can be done by plasmid transfection, for example with our transient AAV system, with a second  TESSA™ vector encoding the AAV genome and gene of interest (which gives more efficient delivery than  transfection), or any alternative existing approach. 

Overall, producing    AAV2 using two  TESSA™ vectors gives approximately a 40-fold increase 
in AAV particle yields compared to the helper free system. We also observe   a >2400 fold cumulative increase in AAV2 infectious  yield ( 1 in 6 genome-containing AAV2 particles is infectious from TESSA, compared to 1 in 1200 from plasmid based transfection; see data below), and an increased percentage of full capsids from 2-5%  up to 70% . 

In the second stage, this AAV seed stock and another TESSA-AAV-Rep-Cap vector can be used to co-infect HEK293 cells. This leads to further AAV replication, so increasing the final AAV yield.   Interestingly, whether you use AAV seed stock generated using two TESSA vectors or  three plasmid transfection,  the  final   AAV yield is  comparable (see data below).

Advantages

TESSA™technology is fully scalable and significantly reduces the number of input materials required for AAV  manufacture. It’s ideally suited for rapid and continuous production of GMP quality AAV, reducing the potential for batch to batch variation. Ultimately, TESSA™ technology will result in improved cost  of goods, and improved safety of gene therapies.  

From our experts to yours: our scientists offer ongoing and detailed technical support so you can have complete confidence in the performance of our technologies once transferred to your own facilities.

Learn more about our proprietary TESSA™ technology.

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