Gene therapies are emerging as promising treatments for previously untreatable genetic disorders, with adeno-associated viruses (AAVs) being the preferred vector for gene delivery. However, AAV-based gene therapies face challenges in production, including cost, complexity, and scalability. With the gene therapy market projected to grow significantly, drug developers are seeking platforms that streamline AAV production. Key factors include ensuring flexibility to accommodate different therapies, minimizing risks by understanding the entire process, and scaling production as projects progress. A well-designed AAV platform can enhance efficiency, quality, and regulatory compliance, ensuring safe delivery of therapies to patients.
Guided by standardized production and purification platforms, developers of monoclonal antibodies (mAbs) and other recombinant-protein therapeutics can take a relatively straightforward path when designing and establishing facilities for commercial-scale operations. By contrast, designing gene-therapy (GT) facilities involves a more complex calculus. Multiple approaches are available for producing transgene-bearing viral vectors at commercial scales. GT developers must choose carefully, knowing that each manufacturing strategy raises distinctive advantages and limitations for process scalability, equipment implementation, storage, material and personnel flow, and ultimately, facility output. The plurality of manufacturing strategies — and the possibility of further platform advancements — requires GT companies and their facility-design teams to be forward-thinking in their planning. All the while, GT facilities must be engineered for good manufacturing practice (GMP) operations and work with viral vectors...
+1The field of bioprocess development has witnessed remarkable advancements in recent years driven by increasing demand for biopharmaceuticals, including gene-therapy products such as recombinant adenoassociated virus (rAAV) vectors. To date, global regulatory bodies have approved several rAAV-based gene therapies, and multiple clinical trials are ongoing as forecasts project significant growth over the next five to 10 years
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The field of rAAV production continues to be dominated by platforms using human embryonic kidney (HEK) and insect cells. For instance, uniQure’s proprietary platform is based on insect-cell production and a baculovirus expression vector system (BEVS)
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. As the gene-therapy clinical pipeline expands, ensuring efficient, cost-effective, and scalable processes for viral-vector production becomes critical
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. Central to that endeavor are scale-down models and fast-paced scale-up.
Scale-down models are small-scale representations that are designed to mimic key process paramet...
+5 The term gene therapy (GT) encompasses a range of strategies for modifying or influencing genetic information either to treat or to prevent disease. GTs include both systems that work by introducing, replacing, or altering the existing genetic material within a patient’s cells — often called gene-modified cell therapy when performed ex vivo — and those that use genetic material to influence or modulate the in vivo expression of genes. Probably for mechanistic reasons, other emerging therapies such as viral oncolytics sometimes are included in GT discussions. It’s helpful to understand that categorical statements regarding many aspects of GT can be difficult because of exceptions to some stated generalities about components and desired functions.
Some GTs involve genetic engineering systems as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). The combination provides a powerful gene-editing tool for precise and permanent modification of DNA sequences...
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