SBIR Phase I: Intracellular Delivery for Rapid Point-of-Care Labeling of Therapeutic Cells

SBIR 第一阶段：用于治疗细胞快速护理点标记的细胞内递送

• 批准号: 2151702
• 负责人: Mark Stolowitz
• 金额: $ 25.55万
• 依托单位: VISICELL MEDICAL INC.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2151702&HistoricalAwards=false
• 关键词: SBIR; Phase; Intracellular; Delivery; Rapid

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project involves leveraging an innovative approach to deliver and monitor therapeutics more effectively. Real-time monitoring and tracking of immune and stem cell therapies is in its infancy. However, without the capability to precisely know where therapeutic cells localize, clinicians cannot assess safety, design optimal doses, or make clinical decisions related to therapeutic approaches. As the multi-billion-dollar cell therapy market is expanding rapidly in its race to develop the next generation of life-saving, cost-effective, lower toxicity cell therapy products there is a heightened requirement for safety risk management to monitor on-target, on-tumor delivery of cell products in patients. This proposal addresses a critical unmet need in the cell and gene therapy industry for rapid point-of-care labeling of therapeutic cells specifically to enable tracking in the body. The addressable market for preclinical and clinical cell tracking in clinical trials involving therapeutic cells in the United States is estimated to reach approximately $1.14 billion by 2024.This Small Business Innovation Research (SBIR) Phase I project involves an innovative approach to intracellular delivery where mechanoporation or cell-squeezing is achieved simply by propelling cells, in the presence of exogeneous cargo, through a proprietary mechanoporation element that resides in a column designed to be processed in a centrifuge (spin column). End users will realize significant advantages over conventional and microfluidic approaches to intracellular delivery including: 1) Convenient spin column format; 2) Short cell processing times; 3) Ease of scale-up and multiplexing; 4) Applicability to numerous cell types; and 5) Compatibility with automated/robotic cell production systems including autologous cell production systems designed for clinical settings. Three objectives are proposed involving the generation of prototype spin columns and their use in optimizing aspects of element design to afford efficient intermolecular delivery of iron-based nanoparticles (magnetic resonance imaging contrast agent) into T-cells and Mesenchymal Stem Cells. The study will enable rapid point-of-care labeling of therapeutic and regenerative cells for in vivo tracking, empowering clinicians to make timely decisions with respect to treatment strategies, thus ensuring better clinical outcomes.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.

这个小企业创新研究（SBIR）第一阶段项目的更广泛的影响/商业潜力涉及利用创新方法更有效地提供和监测治疗。免疫和干细胞疗法的实时监测和跟踪尚处于起步阶段。然而，如果没有能力精确地知道治疗细胞定位在哪里，临床医生就无法评估安全性、设计最佳剂量或做出与治疗方法相关的临床决策。随着数十亿美元的细胞治疗市场在开发下一代挽救生命、具有成本效益、毒性较低的细胞治疗产品的竞争中迅速扩大，对安全风险管理的需求越来越高，以监测细胞产品在患者体内的靶向、肿瘤递送。该提案解决了细胞和基因治疗行业对治疗细胞的快速即时标记的关键未满足需求，特别是能够在体内进行跟踪。到2024年，美国涉及治疗细胞的临床试验中的临床前和临床细胞跟踪的可寻址市场估计将达到约11.4亿美元。这个小企业创新研究（SBIR）第一阶段项目涉及一种创新的细胞内递送方法，其中机械穿孔或细胞挤压仅通过在外源性货物存在下推动细胞来实现，通过专有的机械穿孔元件，该元件位于设计用于在离心机（旋转柱）中处理的柱中。最终用户将认识到与细胞内递送的常规和微流体方法相比的显著优点，包括：1）方便的旋转柱形式; 2）短的细胞处理时间; 3）易于放大和多路复用; 4）适用于多种细胞类型;以及5）与自动化/机器人细胞生产系统（包括为临床环境设计的自体细胞生产系统）的兼容性。提出了三个目标，涉及原型旋转柱的生成及其在优化元件设计方面的用途，以提供铁基纳米颗粒（磁共振成像造影剂）到T细胞和间充质干细胞中的有效分子间递送。该研究将使治疗和再生细胞的快速护理点标记用于体内跟踪，使临床医生能够及时做出治疗策略的决定，从而确保更好的临床结果。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。