Sbir phase II: non-chromatographic method for the purification of viral vectors

This $902,504 cooperative agreement from the National Science Foundation Division of Industrial Innovation under the Engineering program (CFDA 47.041) supports the development of a scalable downstream purification process for gene therapy vectors by Isolere Bio, Inc. of Durham, North Carolina. The non-chromatographic method seeks to address current inefficiencies that lead to single digit yields by utilizing a polypeptide-based reagent combining affinity capture with phase separation and filtration equipment. Validation activities will optimize a tangential flow filtration process across various adenovirus serotypes and impurity levels to demonstrate broad compatibility. Additional work will further explore reagent stabilization of adenovirus and establish manufacturing for consistent, low-cost supply to support clinical development and rapidly deployable adenovirus vaccine manufacturing. Completion is expected to yield a mature one-step adenovirus purification process and quality reagents to advance this sector hampered by existing manufacturing challenges.

Abstract

The broader impact /commercial potential of this small business innovation research (sbir) phase II project is the creation of a scalable platform technology to deliver new therapies and vaccines through manufacturing viral vectors. This sector has been hampered by inefficient manufacturing methods designed for small molecules 10,000 times less complex than the current effort. The technology developed herein will provide a durable competitive advantage by offering ?plug and play,? Broad compatibility, and improved productivity for virus manufacturing compared to existing industry solutions. The technology will improve yields, shorten manufacturing lead times, and accelerate time-to-market for potentially life-saving therapies and vaccines. This research project seeks to validate scalability and establish a production method to deliver quality reagents to developers of adenoviral vectors. This small business innovation research (sbir) phase II project seeks to advance a scalable downstream purification process for gene therapy vectors. Viral vectors have remarkable utility as therapeutics and vaccines, but their impact has been plagued by downstream purification inefficiencies that lead to single digit yields. The technology developed in this project will address this bottleneck using a polypeptide-based reagent that combines affinity-capture with phase separation and filtration equipment. The technology aims to improve capacity, step yield, final vector purity, and productivity. To validate the lead adenovirus reagent, a tangential flow filtration process will be optimized using harvests with a wide range of starting impurities and across various adenovirus serotypes to ensure a broadly compatible product. The reagent?s ability to stabilize adenovirus will be further explored toward an efficient and scalable filtration process. Finally, a method for reagent manufacturing will be developed to ensure consistent and low-cost supply. Completion of these objectives will yield a mature downstream process for one-step adenovirus purification, a manufacturing method that ensures sufficient quantity of quality reagents to support adenovirus clinical development, and rapidly deployable adenovirus vaccine manufacturing to meet future needs. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.