SBIR Phase II: Non-Chromatographic Method for the Purification of Viral Vectors

这个小型企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是创建一个可扩展的平台技术，通过制造病毒载体来提供新的疗法和疫苗。这一领域一直受到低效率的制造方法的阻碍，这些方法是为比目前的努力复杂10，000倍的小分子设计的。与现有的行业解决方案相比，本文开发的技术将通过提供“即插即用”、广泛的兼容性和提高的病毒制造生产率来提供持久的竞争优势。该技术将提高产量，缩短生产周期，并加快潜在的拯救生命的疗法和疫苗的上市时间。该研究项目旨在验证可扩展性，并建立一种生产方法，为腺病毒载体的开发人员提供优质试剂。 这个小型企业创新研究（SBIR）第二阶段项目旨在推进基因治疗载体的可扩展下游纯化过程。 病毒载体作为治疗剂和疫苗具有显著的实用性，但其影响受到下游纯化效率低下的困扰，导致单位数的产率。 该项目开发的技术将使用基于多肽的试剂解决这一瓶颈，该试剂将亲和捕获与相分离和过滤设备相结合。该技术旨在提高产能、步骤产率、最终载体纯度和生产率。为了验证主要腺病毒试剂，将使用具有广泛起始杂质和各种腺病毒血清型的收获物优化切向流过滤工艺，以确保产品具有广泛的相容性。将进一步探索试剂稳定腺病毒的能力，以实现有效和可扩展的过滤过程。最后，将开发一种试剂生产方法，以确保持续和低成本的供应。这些目标的完成将产生用于一步腺病毒纯化的成熟下游工艺，这是一种确保足够数量的优质试剂以支持腺病毒临床开发的制造方法，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查进行评估，被认为值得支持的搜索.

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.