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

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/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，由于无法精确了解治疗细胞的定位，临床医生无法评估安全性，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、低毒性细胞治疗产品的竞赛中迅速扩大，对安全风险管理的要求越来越高，以监测细胞产品在患者体内的靶向、肿瘤上的递送。该提案解决了细胞和基因治疗行业中一个关键的未满足的需求，即治疗细胞的快速即时标记，以便在体内进行跟踪。到2024年，美国涉及治疗细胞的临床试验的临床前和临床细胞跟踪的潜在市场估计将达到约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输送方法，在外来货物存在的情况下，通过一个专有的机械加工元件，在离心机（旋转柱）中进行处理，通过推动细胞来实现机械加工或细胞挤压。最终用户将意识到比传统和微流体方法在细胞内递送方面的显着优势，包括：1)方便的旋转柱格式；2)细胞处理时间短；3)易于扩展和多路复用；4)适用于多种细胞类型；5)与自动化/机器人细胞生产系统的兼容性，包括为临床环境设计的自体细胞生产系统。提出了三个目标，包括生成原型自旋柱及其在优化元件设计方面的应用，以提供铁基纳米颗粒（磁共振成像造影剂）进入t细胞和间充质干细胞的有效分子间递送。该研究将使治疗和再生细胞的快速护理标记能够用于体内跟踪，使临床医生能够及时制定治疗策略，从而确保更好的临床结果。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 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.