Treatment to cure: Advancing AAV gene therapy manufacture

Advanced therapy medicinal products are a reality. With the opportunity to treat patients at the genetic level, the pharmaceutical industry has extended the treatment paradigm to innovative and potentially curative approaches. Gene therapy modifies or manipulates the expression of a gene, through gene repair, replacement, or modification, to alter living cells for therapeutic use, requiring delivery mechanisms through viral vectors. Market analysis not only demonstrates that the gene therapy sector has strong growth potential, but also indicates infancy with the number of currently approved products. Within gene therapy, adeno-associated viruses (AAVs) have high prominence, allowing for the targeted delivery of a transgene for therapeutic effect. To be able to realise the full potential of AAV-based gene therapy, focus has shifted to the ability to manufacture and deliver high titre, high quality, and efficacious product. However, manufacturing is not simple, with multiple complex challenges ranging from starting material generation, ensuring cellular production of high titres of viral vectors, to purification, where not all AAV particles contain the intended genetic payload. As an industry, we must learn from established manufacturing processes, such as for monoclonal antibodies (mAbs), to deliver rapidly scalable, robust, and cost-effective platform solutions that can be truly multiproduct, while working hand-in-hand with regulatory agencies. Additionally future innovation remains important and there are several opportunities for disruptive and further advanced manufacturing approaches. With a true end in mind approach, can we turn the tide from treatment to cure?