OXGENE, a biotechnology company designing and developing scalable gene therapy technologies, has launched its scalable, plasmid-free manufacturing system for AAV. OXGENE’s new TESSA technology addresses industrywide challenges associated with robust and reproducible AAV manufacture at scale. 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, favourable 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 serious challenge to regulators and health authorities when it comes to approving these treatments for clinical use.
OXGENE’s 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.
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.
For more information, visit: www.oxgene.com/TESSA
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Mogrify, a UK company aiming to transform the development of ex vivo cell therapies and pioneer the field of in vivo reprogramming therapies, has launched EpiMOGRIFY. The platform models the epigenetic state of the cell to predict the switches important for cell identity, cell maintenance, directed differentiation and cell conversion.
EpiMOGRIFY is an extension of the Company’s proprietary direct cellular conversion technology, MOGRIFY, and enables the identification of the optimal culture conditions required to maintain cells in chemically defined media. This can be applied in cGMP manufacture and enhances directed differentiation or cell conversion to support the development of scalable off-the-shelf therapies for diseases with a high unmet clinical need.
EpiMOGRIFY combines gene-regulatory information with a model of a cell’s epigenetic landscape and leverages changes in the level of DNA-histone methylation (H3K4me3 modifications). The platform utilizes data from more than 100 human cell/tissue types (available via the ENCODE and Epigenome Roadmap consortia) to accurately define culture conditions that can maintain the cell identity or induce cell conversion.
The predictive power of EpiMOGRIFY has been validated in two ways: cell maintenance and differentiation. EpiMOGRIFY-predicted factors are able to maintain astrocytes and cardiomyocytes in vitro in chemically defined media and promote the generation of astrocytes and cardiomyocytes from neural progenitors and embryonic stem cells, respectively. In both cell maintenance and differentiation, EpiMOGRIFY defined conditions performed as well as or better in all cases when compared to existing undefined conditions, significantly increasing cell growth and survival, as well as resulting in a higher differentiation efficiency.
For more information, visit: https://mogrify.co.uk/science/#epimogrify
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