Flexible Platform for End-to-end Manufacturing of Gene Therapies to Advance Development of Treatments for Ultra-rare Diseases

The success of gene therapies for addressing inherited disorders has been demonstrated by FDA’s approval of AAV-based LUXTURNA® and ZOLGENSMA®. There is great hope that gene therapies will be able to address more of the 10,000+ monogenic diseases that have been identified to date. Gene therapy developers face challenges in cost and access to manufacturing capacity to produce their products. Developers of treatments for ultra-rare genetic diseases, which occur in less than one person per million, are especially disadvantaged as these therapies are not typically of commercial interest to biopharmaceutical manufacturers. Innovations in small-scale manufacturing technologies are urgently needed to fill this gap. We are developing a flexible, cost-efficient, end-to-end manufacturing platform for the production of a small number of doses of AAV gene therapy products.

Additionally, our platform addresses the need for innovation in downstream purification of AAV products.  Current vector purification approaches require specialized equipment which may not be readily available in the standard laboratory. We will develop a novel downstream purification method based on electro-kinetic separation which greatly simplifies elimination of empty AAV capsids. Finally, as the supply of GMP-grade plasmid needed for the triple transfection process can also be a bottleneck, as well as a significant expense, we will demonstrate that our platform is capable of incorporating plasmid manufacturing, including production and purification, to provide an end-to-end solution to the generation of new AAV therapies.