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

SBIR 第二阶段：病毒载体纯化的非色谱方法

• 批准号: 2132838
• 负责人: Kelli Luginbuhl
• 金额: $ 90.25万
• 依托单位: Isolere Bio, Inc
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2132838&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Non; Chromatographic

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.

这项小型企业创新研究（SBIR）II期项目的更广泛的影响 /商业潜力是创建可扩展的平台技术，以通过制造病毒向量提供新的疗法和疫苗。该部门被为小分子设计的效率低下的制造方法妨碍了10,000倍的复杂性，比目前的努力少了10,000倍。与现有行业解决方案相比，此处开发的技术将通过提供“插头和游戏”，广泛的兼容性以及改善病毒制造的生产力来提供持久的竞争优势。该技术将提高产量，较短的制造业时间时间，并加速上市时间，以挽救生命的疗法和疫苗。该研究项目旨在验证可扩展性并建立一种生产方法，以向腺病毒载体的开发商提供质量试剂。这项小型企业创新研究（SBIR）II期项目旨在推进基因治疗载体的可扩展下游纯化过程。病毒载体作为治疗和疫苗具有显着的效用，但是它们的影响受到下游纯化无效的效果的困扰，导致单位数量产量。该项目开发的技术将使用基于多肽的试剂与相位分离和过滤设备相结合的基于多肽的试剂来解决这一瓶颈。该技术旨在验证铅腺病毒试剂，使用具有广泛的起始杂质和各种腺病毒血清型的收获来优化切向流过滤过程，以确保广泛兼容的产品。试剂稳定腺病毒的能力将进一步探讨有效且可扩展的过滤过程。最后，将开发一种试剂制造方法，以确保一致且低成本的供应。这些目标的完成将产生一步腺病毒纯化的成熟下游过程，这是一种制造方法，可确保足够数量的质量试剂来支持腺病毒临床开发，并迅速使用可部署的腺病毒疫苗制造，以满足未来的奖励。 标准。

项目成果

Disruptive bench-scale purification of lentivirus using affinity-liquid phase separation technology

使用亲和液相分离技术对慢病毒进行破坏性小规模纯化

• DOI: 10.18609/cgti.2023.163
• 发表时间: 2023
• 期刊: Cell and Gene Therapy Insights
• 作者: L Votaw, Nicole;Callander, Melissa;Broer, Torie;Wheeler, Alyssa;Dzuricky, Michael;Luginbuhl, Kelli
• 通讯作者: Luginbuhl, Kelli