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

小型企业创新研究(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。这一领域一直受到为小分子设计的低效制造方法的阻碍，这些小分子的复杂性比目前的努力低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，缩短制造周期，并加快潜在挽救生命的疗法和疫苗的上市时间。该研究项目旨在验证可伸缩性，并建立一种生产方法，以向腺病毒载体的开发者提供高质量的试剂。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。病毒载体具有显著的治疗和疫苗效用，但它们的影响一直受到下游净化效率低下的困扰，导致产量达到个位数。该项目开发的技术将使用一种基于多肽的试剂来解决这一瓶颈，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、步长产量、最终载体纯度和生产率。为了验证先导腺病毒试剂，切向流过滤过程将使用具有广泛起始杂质的收获并跨各种腺病毒血清型进行优化，以确保产品具有广泛的兼容性。该试剂稳定腺病毒的能力将进一步探索，以实现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一步提纯腺病毒的成熟下游工艺，一种确保足够数量的高质量试剂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制造以满足未来需求。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.