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

这个小企业创新研究（SBIR）第二阶段项目的更广泛影响/商业潜力是创建一个可扩展的平台技术，通过制造病毒载体提供新的疗法和疫苗。这一领域一直受到效率低下的制造方法的阻碍，这些方法是为小分子设计的，比目前的努力要简单1万倍。与现有的行业解决方案相比，这里开发的技术将提供“即插即用”、广泛的兼容性和更高的病毒制造生产率，从而提供持久的竞争优势。这项技术将提高产量，缩短生产周期，加快可能挽救生命的疗法和疫苗的上市时间。本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高质量的试剂。这项小型企业创新研究（SBIR）二期项目旨在推进可扩展的下游基因治疗载体纯化过程。病毒载体作为治疗和疫苗具有显著的效用，但其影响一直受到下游净化效率低下的困扰，导致产量只有个位数。本项目开发的技术将利用多肽基试剂解决这一瓶颈，该试剂结合了亲和捕获与相分离和过滤设备。该技术旨在提高产能、步产量、最终载体纯度和生产力。为了验证先导腺病毒试剂，切向流过滤过程将使用广泛的起始杂质和不同的腺病毒血清型进行优化，以确保广泛兼容的产品。该试剂稳定腺病毒的能力将进一步探索高效和可扩展的过滤过程。最后，将开发一种试剂制造方法，以确保一致和低成本的供应。这些目标的完成将产生成熟的一步腺病毒纯化下游工艺，一种确保足够数量的高质量试剂以支持腺病毒临床开发的制造方法，以及快速部署的腺病毒疫苗生产以满足未来需求。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.